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Columbia  Wini\itx&itp 
intijeCitpofi^efaoPorfe 

College  of  ^Ijpgicians  anb  burgeons! 


i^eference  Hihvavp 


THE  BACTERIAL  DISEASES 

OF   RESPIRATION,   AND 

VACCINES  IN  THEIR 

TREATMENT 


R.    W.    ALLEN,   M.D.,    B.S.(Lond.) 

LATE    EDITOR,    'JOURNAL    OF    VACCINE    THERAPY*;      LATE    CLINICAL    PATHOLOGIST 

TO     THE     MOUNT     VERNON     HOSPITAL     FOR     DISEASES     OF     THE     CHEST; 

LATE     PATHOLOGIST     TO     THE     ROYAL    EYE     HOSPITAL  ;      LATE 

GULL    STUDENT    OF    PATHOLOGY,    GUV's    HOSPITAL 


Printed  in  En,s;land  ] 


PHILADELPHIA 

P.    BLAKISTON'S    SON    &    CO. 

IOI2   WALNUT   STREET 
1913 


PREFACE 

A  /r  OST  of  the  matter  herein  contained  has  already  appeared  as  a 
series  of  articles  in  the  numbers  of  the  Journal  of  Vaccine 
Therapy  from  February,  igi2  to  January,  1913  inclusive.  These 
have  been  revised  and  fresh  matter  included,  the  most  important 
additions  being  in  the  sections  devoted  to  pulmonary  tuberculosis. 
Chapter  XI  is  entirely  new.  My  endeavour  has  been  to  treat  my 
subjects  in  as  practical  a  manner  as  possible  ;  to  lay  before  my  readers 
the  various  considerations  which  should  influence  them  in  seeking  help 
from  specific  treatment ;  and  to  point  out  those  methods  of  application 
which  a  considerable  practical  experience  has  convinced  me  yield  the 
best  results. 

To  Dr.  Ralph  Vincent  I  am  greatly  indebted  for  taking  the 
numerous  excellent  photographs  and  photo-micrographs  which  illus- 
trate this  book. 

128.  Harley  Street  ; 
Jainiary,  1913. 


Digitized  by  the  Internet  Archive 

in  2010  with  funding  from 

Open  Knowledge  Commons 


http://www.archive.org/details/bacterialdiseaseOOalle 


CONTENTS 


PAGE 

Introduction        .........  i 

CHAPTER    I. 

The  Bacteriology  of  the  Respiratory  Tract  in  Health        .  .  4 

CHAPTER    II. 

The  Respiratory  Tract  in  Disease— Methods  of  Investigation- 
Technique  OF  various  Staining  Methods       ....  8 

CHAPTER    III. 

Cultural  Methods  for  Investigating  the  Bacteriology  of  the 
Respiratory  Tract — Description  (with  Plates)  of  the  various 
Pathogenic  Bacteria  which  may  be  present  .  .  .23 

CHAPTER    IV. 

Results  of  Observations  into  the  Bacteriology  of  the  various 
Diseased  Conditions  of  the  Respiratory  Tract— Nasal  and 
Post-nasal  Catarrh — Diseases  of  the  Accessory  Sinuses — 
Eustachian  Catarrh  and  Otitis  Media — Tracheitis  and  Laryn- 
gitis— Pulmonary  Catarrh,  Bronchitis  and  Asthma — Whooping- 
Cough — Pulmonary  Phthisis       ......        42 

CHAPTER   V. 

The  Vaccine  Therapy  of  Respiratory  Disorders — General  Con- 
siderations— Control  of  Dosage  and  Intervals — Special  Con- 
siderations— Preparation  and  Administration  of  the  Vaccine        58 

CHAPTER    VI. 

Vaccines  in  the  Treatment  of  Nasal  and  Post-nasal  Catarrh, 
Tracheitis  and  Laryngitis,  and  Infections  of  the  Accessory 
Spaces  ........  -79 


X  CONTENTS. 

PAGE 

CHAPTER    VII. 
Vaccines  in  the  Treatment  of  Bronchitis  and  Asthma          .  .        90 

CHAPTER    VIII. 

Vaccines  in  Pneumonia— Bacteriology — Prophylaxis — The  Patho- 
logy AND  ITS  Bearing  on  Vaccine  Treatment  :  Technique  and 
Results — Unresolved  Pneumonia— Empyema  and  Lung  Abscess 
—Broncho-Pneumonia        .......      103 

CHAPTER    IX. 

Vaccines   in  Whooping-Cough,   Diphtheria,   Pyorrhoea  alveolaris, 

Hay-Fever,  Ozjena,  Rhinoscleroma       .  .  .  .  .121 

CHAPTER    X. 

The  Mixed  Infections  of  Pulmonary  Tuberculosis  and  Vaccines 
in  their  Treatment — Import  of  Mixed  Infection — Technique 
OF  Specific  Therapy — Results— Prophylaxis  .  .  .      140 

CHAPTER    XI. 

Infections  by  the  Tubercle  Bacillus  and  the  Use  of  Specific 
Products  in  their  Treatment— The  Tubercle  Bacillus  and 
its  Toxins— The  Defensive  Mechanism  of  the  Body— The  Tuber- 
culins AND  their  Use  in  the  Diagnosis  of  Pulmonary  Tuber- 
culosis :  The  Various  "Tests"  — Classification  of  Cases  of 
Pulmonary  Tuberculosis— Choice  of  Tuberculin— Control  of 
Dosage  and  Intervals — Treatment  by  the  Induction  and 
Control  of  Auto-inoculations— Conclusion  .  .  .  .192 

INDEX. 


THE  BACTERIAL  DISEASES  OF  RESPIRATION, 
AND  VACCINES  IN  THEIR  TREATMENT. 


INTRODUCTION. 

When  first  I  began  the  study  of  this  question  just  ten  years  ago, 
the  one  thing  that  struck  me  beyond  all  others  was  the  utter  inadequacy 
of  the  information  obtainable  from  works  in  the  English  language, 
and,  indeed,  in  any  tongue,  -either  bacteriological  or  dealing  with 
general  medicine,  upon  this  very  important  subject.  Despite  the  great 
impetus  given  to  exact  bacteriological  research  by  the  developments  of 
vaccine  therapeutics,  especially  within  the  past  five  years,  the  omission 
has  not  yet  been  repaired  in  any  single  book  or  collection  of  books  to 
which  I  have  had  access.  The  true  importance  of  any  disease  is  to  be 
estimated  neither  by  its  rarity  nor  by  its  mortality-rate,  but  rather  by 
its  frequency  and  its  disabling  power.  Granting  the  truth  of  this 
statement,  it  follows  that  diseases  of  the  respiratory  tract  are  of 
supreme  importance  to  the  human  race ;  in  frequency  they  excel  all 
others,  in  the  production  of  impaired  health  of  varying  periods  and  to 
varying  extents  they  are  fruitful  to  an  extreme  degree.  It  has  occurred 
to  me  that  a  brief  but  systematic  description  of  the  bacterial  diseases 
of  the  respiratory  tract  would  have  a  certain  value  and  prove  of  interest 
to  many.  This  I  shall  endeavour  to  carry  out  according  to  the 
following  scheme."^ 

A.  The  Respiratory  Tract  in  Health. 

(i)    Post-mortem  results. 

(ii)    Results  obtained  during  life  ;  methods  ;  carriers. 

B.  The  Respiratory  Tract  in  Disease. 

(i)    Methods  of  investigation. 

*   For  the  photographs  and  photo-micrographs   I  am  entirely  indebted  to  the  kindness 
of  Dr.  Ralph  Vincent. 

I 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

(a)  Swabs  from  nose  ;  precautions  necessary  in  taking 
from  turbinal  bones,  antra  and  sinuses. 

(6)  Secretion  from  nose;  precautions  necessary  in 
collecting. 

(c)  Swabs  from  throat  and  Eustachian  tubes ;  necessity 

of  excluding  or  allowing  for  presence  of  pyorrhcea 
alveolaris,  or  tonsillitis  (follicular  or  otherwise). 

(d)  Sputum  ;  precautions  necessary  in  collecting. 
{e)    Lung  puncture. 

(/)  Examination  of  the  specimen. 

(i)   Chemical  determination  of  source  ;  salol  test ; 
albumen  test. 

(2)  Staining  methods  for  cells  and  bacteria. 

(3)  Cultural  methods. 

(ii)  Description  of  the  bacteria  which  may  be  present  : 

Tubercle  bacillus,  *lepra  bacillus,  ^Streptothrix  actinomy- 
cosis, *Spiroch(2ta  pallida,  *Staphylococctis  albus,  aureus, 
citreus,  candicans,  Streptococcus  group,  pneumococcus, 
B.  influenzcB,  B.  Bordet-Gengou  of  whooping-cough, 
*bacillus  of  Koch-Weeks,  B.  diphtherice,  "^S.  Hoffinanii, 
*B.  xerosis,  B.  septiis,  M.  catarrhalis  group,  M.  para- 
tetragenus,  M.  tetragenus,  bacillus  of  Friedlander  group, 
B.proteus  group,  B.  pyocyaneus,  B.  coli,  B.  typhosus, 
■^various  organisms  associated  with  pyorrhoea  alveolaris 
and  tonsilhtis,  such  as  vibrios,  streptothrices,  micro- 
cocci and  fusiform  bacilli,  t  B.  ozcsnce,  t  B.  of  rhino- 
scleroma. 

*  To  these  bacteria  short  reference  only  will  be  made. 

t  For  description  of  these  bacteria  see  Chapter  IX. 

(iii)  Results  of  observations. 

(i)  In  nasal  and  post- nasal  catarrh. 

(2)  In  diseases  of  the  accessory  sinuses. 

(3)  In  Eustachian  catarrh  and  otitis  media. 

(4)  In  tracheitis  and  laryngitis. 

(5)  In  pulmonary  catarrh,  bronchitis  and  asthma. 

(6)  In  whooping-cough. 

(7)  In  pulmonary  phthisis. 

(iv)  Vaccine  therapy  of  respiratory  disorders. 

(a)  General  considerations. 

(b)  Special  considerations. 

(i)  Nasal  and  post-nasal  catarrh,  tracheitis  and  laryn- 
gitis, and  infections  of  the  accessory  spaces. 
(2)  Bronchitis  and  asthma. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  3 

(3)  Pneumonia. 

(4)  Whooping-cough. 

(5)  Diphtheria. 

(6)  Pyorrhcea  alveolaris. 

(7)  Hay  fever. 

(8)  Ozsena  or  atrophic  rhinitis. 
(g)  Rhinoscleroma. 

(10)   Pulmonary  tuberculosis. 

(a)  Mixed  infections  :  their  import  and  treatment. 

(b)  Infection  by  the  tubercle  bacillus  and  the  use 

of  specific  products  in  treatment. 


CHAPTER    I. 

A.  THE    BACTERIOLOGY    OF  THE  RESPIRATORY  TRACT 

IN    HEALTH. 

It  is  only  those  who  have  devoted  years  to  research  in  one  of  the 
"exact  sciences,"  such  as  physics  or  physical  chemistry,  who  can 
adequately  realise  the  supreme  importance  to  any  investigation 
of  the  performance  of  sufficient  "  control "  observations.  It  is 
owing  to  the  peculiar  difficulty  in  securing  subjects  which  can  in 
any  way  be  regarded  as  absolutely  normal  or  healthy  individuals,  and 
as  suitable,  therefore,  to  act  as  "controls,"  that  medicine  has  failed 
in  the  past,  and,  perforce,  will  fail  in  the  future,  to  take  a  place  among 
the  exact  sciences.  The  multiplication  of  careful  control  observations 
upon  individuals  as  healthy  as  can  be  obtained  in  regard  to  the  parts 
under  study  serves  to  a  considerable  degree  to  eliminate  erroneous 
conclusions. 

The  artificial  conditions  of  modern  life  have  rendered  it  peculiarly 
difficult  to  secure  for  investigation  an  adequate  number  of  individuals 
any  part  of  whose  respiratory  tracts  could  be  regarded  as  strictly 
healthy,  especially  from  the  bacteriological  standpoint.  It  may  be 
recalled  that  some  people  appear  constantly  to  harbour  the  Micrococcus 
catarrhalis  in  their  nasal  passages,  yet  only  very  occasionally  suffer 
from  acute  nasal  catarrh,  and  then  for  strictly  limited  periods  only, 
whilst  from  the  throats  of  others  the  pneumococcus  or  Bacillus 
diphthericB  can  be  constantly  recovered,  yet  never  have  they  suffered 
from  pneumonia  on  the  one  hand  or  diphtheria  on  the  other.  The 
study  of  these  so-called  "  carriers  "  would  tend  to  the  conclusion  that 
these,  therefore,  could  not  be  pathogenic  bacteria,  yet  the  contrary  we 
know  to  be  the  case. 

It  is  perhaps  fortunate  that  the  results  of  vaccine  treatm.ent  in 
diseases  of  the  respiratory  tract  enable  us  to  confirm  deductions  made 
from  observations  inherently  fallacious  and  difficult  to  control. 

In  any  bacteriological  research  it  is  above  all  essential  that  two 
conditions   be  fulfilled  :    (i)   that   the   material    be  obtained  from    the 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  5 

desired  situation  without  chance  of  contamination  in  the  process  ;  (2) 
that  it  be  speedily  prepared  in  film  form  for  direct  examination  ;  this 
done,  that  it  be  immediately  transferred  to  suitable  media  for  cultural 
observation.  By  suitable  media  is  meant  such  as  each  and  ever\'  one  of 
the  bacteria  present  may  find  adapted  to  their  growth. 

Through  failure  to  comply  in  one  or  other  direction  with  these 
prime  essentials  practically  all  investigators  upon  the  respiratorv  tract, 
with  the  exception  of  some  who  have  worked  within  the  last  five  or 
six  3-ears,  have  rendered  their  observations  so  untrustworthy  as  to  be 
almost  valueless.  As  the  procedures  adapted  to  the  studv  of  patholo- 
gical conditions  are  a  fortiori  suitable  in  normal  or  healthv  states,  their 
consideration  is  deferred  to  the  next  section  upon  the  bacteriology  of 
the  respirator}-  tract  in  disease. 

Inasmuch  as  many  of  the  domestic  animals,  such  as  cattle,  horses, 
cats,  dosrs,  and  rabbits  are  susceptible  to  respiratory  disorders  like 
those  of  man,  the  comparative  study  of  the  respiratory  systems  of 
these  animals  in  health  and  disease  would  prove  illuminating  ;  unfor- 
tunately this  has  not  been  done,  and  such  information  as  we  have  is 
therefore  incomplete.  Observations  upon  the  dead  human  subject  are 
also  liable  to  prove  very  misleading  owing  to  ''"'agonal  spasms'" 
and  other  causes,  except  in  the  instance  of  those  who  have  died  a 
violent  death  ;  investigation  upon  these  latter  is  wholl}'  lacking. 

The  recent  observations  upon  animals  by  Cobbett  (Proc.  Roy. 
Sac.  Med.,  Jul}',  1911,-  p-  205)  have,  howe\-er.  brought  out  clearly 
one  important  fact.  He  there  states  that  he  has  never  failed  to  find 
bacteria  in  the  lungs  of  the  various  animals  that  he  examined — these 
were  killed  instantaneously  and  examined  at  once  so  that  agonal  and 
post-mortem  infection  can  be  absolutely  excluded.  Among  the  germs 
he  commonly  found  in  the  lungs  of  rabbits  and  guinea-pigs  were 
moulds,  streptothrices,  spore-bearing  bacilli  and  cocci — in  fact,  just  the 
ordinary  micro-organisms  of  the  air.  Spraying  experiments  by  Hurtl 
and  Hermann  and  by  Bastel  and  Neumann  have  been  confirmed  by 
Cobbett.  and  show  that  air-borne  bacteria  freely  enter  the  air-passages 
and  get  carried  to  the  lung ;  the  bronchial  mucous  membrane,  like 
the  intestinal,  must,  therefore,  for  practical  purposes  be  regarded  as 
part  of  the  surface  of  the  body. 

Nor  is  this  the  only  route  whereb\-  bacteria  reach  the  lungs  of  the 
normal  and  so  a  fortiori  of  the  unhealthy  individual.  While  it  is  pro- 
bably true  that  the  various  lymph-glands,  and  especially  the  bronchial, 
cervical  and  abdominal  ones,  are  ver}-  efficient  guardians  of  the  general 
circulatory  system  against  bacterial  infection,  it  yet  certainly  happens 
that  occasionally  bacteria  penetrate  the  defence  and  find  ingress  into 
the    blood-stream.      The  two    organs   in  particular  which   from   their 


6  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

structure  are  peculiarly  adapted  for  the  filtration  of  these  chance 
invaders  are  the  lungs  and  spleen ;  it  thus  happens  that  a  certain 
number  of  bacteria  reach  the  lung  via  the  circulation. 

That  the  air,  especially  of  cities,  is  laden  with  bacteria  is  common 
knowledge  ;  the  proportion  of  pathogenic  to  non-pathogenic  organisms 
is,  however,  small.  Experiments  upon  purely  nose-breathers  has  shown 
that  the  filtration  of  the  air  in  the  nasal  passages  is  efficient  to  an 
extraordinary  degree  ;  the  mouth-breather  loses  this  protective  action, 
and  is  consequently  much  the  more  prone  to  respiratory  disorders.  It 
is  of  obvious  interest  to  know  in  what  part  of  the  nasal  passages  this 
daily  host  of  bacteria  is  stopped  and  what  is  their  fate.  One  fact  upon 
which  all  investigators  are  agreed  is  that  the  vestibule  of  the  nose  is 
swarming  with  bacteria  ;  another  is  that  in  health  the  accessory  air- 
spaces and  the  upper  meatus  of  the  nose  are  approximately  sterile. 
The  precise  degree  of  bacterial  infection  commonly  existent  below  the 
level  of  the  middle  turbinal  has  not  been  accurately  determined  owing 
to  faulty  methods  of  observation.  The  most  satisfactory  published 
investigations  are  those  of  Lewis  and  Logan  Turner  (Edin.  Med.  Journ., 
1905,  vol.  ii,  p.  393).  It  is  to  be  regretted  that  their  cultural  methods 
were  not  beyond  criticism^  the  failure  to  make  an  invariable  rule  of 
employing  blood-agar  as  a  medium  being  a  very  important  omission. 
By  means  of  smears  and  cultures  they  examined  26  specimens  from 
16  persons  ;  only  3  of  these  proved  to  be  sterile. 
13  specimens  from  7  persons  showed  only  one  variety  of  bacterium. 
9  55  >j     7         J5  ,,  two  varieties         ,, 

I  "  5,     I         „  ,,  three       ,,  „ 

Staphylococcus  albus  was  present  in  13  specimens. 

Streptococcus  ,,  6 

Pneumococcus 

Hoffmann's  bacillus 

Staphylococcus  aureus 

Bacillus  niesentericus 

Spirillum 

Bacillus  of  Friedlander 

Proteus  vulgaris 
The  pathogenicity  of  the  organisms  was  determined  upon  rabbits 
and  guinea-pigs  in  eleven  instances — an  investigation,  in  my  opinion, 
entirely  lacking  value  and  only  likely  to  prove  misleading.  Nine  of 
them  appeared  to  be  non-pathogenic,  two  were  pathogenic,  viz,  a 
streptococcus  and  a  Staphylococcus  aureus.  Their  conclusion  was  that 
the  organisms  of  the  healthy  nose  belong  to  the  same  varieties  as  those 
found  in  abnormal  conditions,  but  differ  in  that  they— 
(i)  Are  present  in  much  fewer  numbers. 


,,                      u 

4 

„              2 

,,              2 

jj              2 

jj              2 

„              I 

specimen 

„              I 

J5 

THE    BACTERIAL    DISEASES    OF    RESPIRATION.  7 

(2)  Afford  purer  cultures. 

(3)  Possess  less  vigorous  power  of  growth. 

(4)  Are  of  low  pathogenicity. 

These  observations  are  in  practical  accord  with  my  own,  and  it 
would  appear  that  by  far  the  greater  proportion  of  the  bacteria  which 
enter  the  healthy  nose  are  deposited  in  the  vestibule  and  the  inferior 
meatus. 

Of  their  precise  fate  we  know  little.  Many  are  removed  by  the  use 
of  the  handkerchief;  some  certainly  are  phagocytosed  by  the  epithelial 
cells,  which  possess  this  power  to  a  very  high  degree ;  whether  any 
undergo  lysis  by  the  aid  of  the  mucus  is  unknown.  That  nasal  mucus 
is  absolutely  devoid  of  bactericidal  power  I  showed  some  years  ago  ; 
that  it  may  possess  a  lytic  action  is  possible,  but  appears  not  to 
be  the  case  from  a  number  of  experiments  which  I  have  made  to 
elucidate  this  point. 

Any  attempt  at  discussion  as  to  what  is  the  bacteriology  of  the 
healthy  mouth  would  be  of  purely  academic  interest,  in  as  much  as 
the  perfectly  healthy  mouth  is  for  all  practical  purposes  non-existent. 
Somewhere  or  other  in  every  mouth  or  pharynx  careful  search  will 
reveal  a  focus  of  disease :  it  may  be  a  carious  tooth,  inflamed  dental 
papillae,  a  condition  of  pyorrhoea  alveolaris,  confined  perhaps  to  the 
gum  round  a  wisdom  tooth  or  behind  the  upper  incisors,  follicular 
tonsillitis,  an  infection  of  the  supra-tonsillar  fossa  difficult  of  detection, 
a  granular  pharyngitis  or  some  other  condition  giving  rise  to  little  or  no 
discomfort,  but  none  the  less  surely  there.  A  perusal  of  the  volumi- 
nous writings  upon  the  bacteriology  of  these  conditions  would  lead 
to  but  one  conclusion  :  that  if  one  or  the  other  of  these  conditions  be 
normally  present  in  the  mouth  or  pharynx,  then  so  varied  is  the  bacterial 
content  already  of  the  oral  cavity  that  it  must  surely  be  a  hopeless 
task  to  endeavour  to  elucidate  the  bacteriology  of  any  other  focus  of 
disease  in  or  near  the  mouth  or  pharynx.  In  actual  practice  the  diffi- 
culty is  by  no  means  as  great  as  it  would  appear,  provided  that  due 
recognition  be  paid  to  the  possible  fallacies  thereby  introduced,  and 
measures  be  taken  for  their  exclusion  ;  how  this  can  be  done  will 
appear  presently.  Of  the  organisms  which  have  been  found  in  more 
or  less  normal  oral  cavities  the  following  is  a  very  imperfect  list : 
Staphylococcus  albus  and  aureus,  streptococcus,  Micrococcus  catarrhalis, 
various  small  micrococci,  both  staining  and  failing  to  stain  by  Gram's 
method,  vibrios,  spirilla,  spirochaetas,  fusiform  bacillus,  B.  necrodentalis, 
B.  huccalis  maximus,  Cladothrix  buccalis,  B.  proteus,  B.  inesentericus,  B. 
subtilis,  B.  fluovescens,  sarcinae,  yeasts,  and  moulds. 


CHAPTER    II. 
B.    THE    RESPIRATORY   TRACT    IN    DISEASE. 

(i)  Methods  of  Investigation. 

These  are  to  be  pursued  upon  material  obtained  either  by  oneself  or 
by  one  more  highly  trained  in  the  technique  of  catheterising  the  various 
accessory  air-spaces,  or  else  upon  material  supplied  by  the  patient. 
By  each  and  every  one  of  these  special  precautions  must  be  observed  in 
order  that  the  bacteriological  findings  may  not  be  unduly  obscured. 
Some  of  the  more  important  points  may  here  be  mentioned. 

{a)  In  the  securing  of  "swabs"  from  the  turbinal  bones,  septum, 
antrum,  and  accessory  air-cells  and  Eustachian  tubes  the  nasal  route 
must  perforce  be  adopted.  To  the  fact  that  the  vibrissas,  vestibule  and 
inferior  meatus  are  swarming  with  the  bacteria  caught  up  from  the  air- 
stream  attention  has  been  already  drawn.  It  is  therefore  obvious  (i) 
that  these  bacteria  should  be  removed  as  far  as  possible ;  (2)  that 
contact  with  these  parts  by  the  swab  or  loop  must  be  carefully  avoided. 
The  former  object  is  attained,  for  all  practical  purposes,  by  washing 
the  hands  well  with  hot  water  and  ethereal  soap,  then  by  means  of  the 
finger-tips,  moistened  with  soap  and  hot  sterile  water,  the  orifice  of  the 
nose  is  thoroughly  cleansed ;  a  pledget  of  sterile  wool  moistened 
Mfith  absolute  alcohol  is  employed  to  swab  out  the  orifice.  A  sterilised 
nasal  speculum  is  next  inserted,  and  through  it  the  swab  or  platinum 
loop  is  carefully  passed  and  secretion  taken  up  from  the  desired 
spot.  Adequate  illumination  and  considerable  technical  skill  are 
requisite  if  the  materies  is  to  be  collected  from  the  Eustachian  tube, 
antrum  or  accessory  sinuses.  Particular  care  must  be  directed  to  the 
withdrawal  of  the  swab  or  loop  as  contamination  is  then  particularly 
liable  to  occur.  The  methods  of  examination  of  the  specimen  by 
direct  observation  of  suitably  stained  films  and  by  cultural  examination 
will  be  detailed  later.  Attention  may,  however,  be  drawn  to  this  fact 
that  inasmuch  as  specimens  of  nasal  mucus  frequently  contain  but 
few  organisms,  so  few  as  to  be  difficult  of  detection  in  film  preparations, 
a  sufficiency  of  material  must  be  collected  not  only  for  the  insemination 
of  plates,  but  also  for  the  preparation  of  quite  thick  smears. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  9 

(b)  If  the  specimen  of  mucus  is  to  be  furnished  by  the  patient, 
instruction  must  be  given  in  this  method  of  cleansing  the  nasal  orifice, 
and  two  steriHsed,  wide-necked  bottles  be  supplied :  two  bottles  are 
requisite  for  this  reason,  that  especially  in  cases  of  antral  or  sinus 
infection  the  bacteriology  of  the  two  sides  may  by  no  means  be  the 
same  ;  the  necessity  of  securing  specimens  from  both  sides  is  therefore 
obvious. 

The  patient  receives  the  following  instructions  :  Immediately  on 
waking  the  nose  is  cleansed  as  indicated  above,  the  stopper  removed 
from  one  bottle,  which  is  then  held  against  one  orifice,  the  other  being 
closed  by  means  of  a  finger-tip  ;  a  forcible  nasal  effort  then  expels 
some  of  the  secretion  directly  into  the  bottle,  which  is  at  once 
stoppered.  This  operation  is  repeated  with  the  other  side,  and  the 
specimens  forwarded  for  examination  without  delay. 

(c)  and  [d)  Considerable  as  is  the  care  necessary  for  the  collection 
of  nasal  specimens,  it  is  relatively  quite  inconsiderable  to  that  requisite 
for  the  collection  of  secretion  from  the  naso-pharynx,  pharynx,  and 
lower  respiratory  tract.  Of  all  the  cavities  of  the  body  the  mouth  and 
pharynx  bacteriologically  are  incomparably  the  foulest ;  go  per  cent., 
at  least,  of  all  residents  in  the  United  Kingdom  carry  in  their  mouths 
foci  of  bacterial  infection — undetected  pyorrhoea  alveolaris  ravages 
their  gums,  poisons  them  locally  and  generally,  impairs  the  digestion, 
the  appetite  and  general  health,  produces  chronic  invalids,  gives  rise 
to  obscure  pains  and  pyrexias,  complicates  respiratory  phthisis,  and, 
let  it  well  be  borne  in  mind,  of  itself  produces  a  premature  end  in  by 
no  means  an  inconsiderable  number  of  cases.  Follicular  tonsillitis 
also  frequently  escapes  the  e5/e,  not  only  of  the  patient,  but  likewise  of 
the  medical  man  :  cursory  examination  will  by  no  means  suffice  for  its 
detection,  especially  when  the  follicles  infected  by  those  immediately 
posterior  to  the  anterior  pillar  of  the  fauces  or  those  of  the  supra- 
tonsillar  fossa  ;  careful  pressure  upon  and  around  the  anterior  pillar 
will  frequently  reveal  an  unsuspected  focus  of  infection.  Into  the 
bacteriology  of  these  conditions,  which  is  so  characteristic  as  to  reveal 
their  presence  when  naked-eye  observation  has  defaulted,  I  shall  enter 
fully  later,  but  let  it  here  be  mentioned  that  several  of  the  commoner 
bacterial  agents  of  these  conditions  are  precisely  those  responsible  for 
catarrhs  of  the  respiratory  tract,  colds,  asthma,  bronchitis,  pneumonia, 
and  the  mixed  infections  of  phthisis  ;  others  which  are  not  responsible 
for  these  conditions  also  are  productive  of  extra-cellular  toxins  so 
potent  that  one  minim  of  a  sterilised  broth  culture  injected  sub- 
cutaneously  may  sufiice  to  produce  vomiting  and  rigors. 

When,    therefore,  a   patient    presents  himself  for  treatment  of  a 
respiratory  disorder,  and  pharyngeal,  laryngeal,  or  bronchial  specimens 


lO  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

are  contemplated,  it  behoves  us  first  and  foremost  carefully  to 
scrutinise  the  mouth  and  pharynx ;  to  examine  the  gums,  especially 
behind  the  upper  incisors  and  around  the  back  molars  and  wisdom 
teeth,  for  the  presence  of  pyorrhcea  alveolaris,  the  tonsils  for  inflamed 
and  infected  crypts  and  follicles— and  here  let  me  urge  upon  your 
notice,  crowned  teeth  or  bridges  practically  invariably  indicate  an 
accompanying  pyorrhoea,  for  the  recession  of  the  gum  has  given  ample 
room  for  the  fixation  of  the  denture.  Such  supreme  importance  do  I 
now  attach  to  these  conditions  in  respiratory^disorders,  that  should  I 
detect  their  presence  and  the  patient  refuse  to  have  them  properly 
treated,  then  I  firmly  and  finally  refuse  to  undertake  the  treatment  of 
the  respiratory  condition.  To  allow  oneself  to  be  so  handicapped  at  the 
outset  is  foolish  beyond  measure. 

The  bacterial  content  of  the  mouth  incidental  to  food  residues 
also  needs  elimination.  All  fallacies  introduced  by  the  above  causes 
may  be  satisfactorily  ehminated  by  the  following  procedure,  which 
merely  needs  the  more  careful  performance  should  pyorrhaea  or  ton- 
silitis  have  been  detected.  A  jug  of  well-boiled  water  is  provided,  and  a 
new,  moderately  hard  tooth-brush  taken  and  dipped  for  a  few  seconds 
twice  or  thrice  into  the  boiling  water,  which  is  then  cooled  to  a  com- 
fortable temperature.  The  teeth  are  now  thoroughly  brushed  with  the 
new  brush  and  sterile  water,  no  powder  or  antiseptics  being  employed. 
The  mouth  is  well  rinsed  out  and  the  throat  gargled  with  the  water,  of 
which  two  or  three  mouthfuls  then  are  swallowed.  Swabs  are  now 
taken  from  the  naso-pharynx,  pharynx,  tonsils  or  larynx,  and  employed 
for  direct  and  cultural  examinations  in  the  manner  presently  to  be 
related.  Should  the  area  of  infection  be  too  low  in  the  respiratory 
tract  for  us  to  reach,  the  patient  is  instructed  to  carry  out  the  above 
procedures  immediately  on  waking,  then  give  one,  or  at  the  most  two, 
coughs,  and  expectorate  directly  into  the  wide-necked  sterile  bottle 
with  which  he  has  been  furnished.  If  accurate  bacteriological  in- 
vestigation be  desired,  too  much  stress  can  hardly  be  laid  upon  the  due 
observance  of  these  preliminary  precautions. 

{e)  Lung  puncture. — Occasionally  in  cases  of  suspected  lung  infection 
no  sputum  can  be  voided  for  examination — a  dilemma  in  which  I 
myself  have  been  placed  on  at  least  three  occasions.  Recourse  must 
then  be  had  to  puncture  of  the  lung,  a  procedure  altogether  void  of 
danger  if  due  precautions  be  observed,  but  not  devoid  of  pain.  Briefly, 
the  method  is  as  follows  :  Careful  percussion  and  auscultation  having 
revealed  a  suspected  area  the  skin  is  sterilised,  best  with  strong  tincture 
of  iodine,  and  may  then  be  anaesthetised  with  ethyl  chloride  spray.  A 
5-10  c.c.  all-glass  syringe  with  a  strong  wide  needle  is  sterilised  by 
boiling  and  i  or  2  c.c.  of  sterile  peptone  broth  taken  into  it.     The 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  I  I 

patient  is  then  instructed  to  expire  and  cease  respiratory  movement ; 
in  this  way  tearing  of  lung  tissue  and  resultant  pain  is  minimised.  The 
needle  is  plunged  boldly  into  the  selected  area,  o'5-i"o  c.c.  of  the  broth 
expelled,  and  gentle  aspiration  applied ;  if  necessary  the  needle  may  be 
withdrawn  a  little  or  inserted  further  and  the  procedure  repeated.  The 
specimen  so  obtained  is  to  be  examined  by  direct  and  cultural  observa- 
tion ;  the  results  are  very  satisfactory  as  risk  of  contamination  is 
minimal ;  in  this  way  I  have  secured  cultures  of  B.  influenzce, 
pneumococcus,  and  B.  typhosus  directly  from  the  lung. 

(f)  Examination  of  the  materies  morbi  :  (i)  Chemical  determination  of 
source. — The  mere  bacteriological  examination,  direct  and  cultural,  will 
not  suffice  for  all  cases.  To  enter  into  a  full  discussion  of  the  con- 
stituents of  the  sputum  and  nasal  secretion  would  be  beyond  the  scope 
of  this  paper;  attention  may,  however,  be  briefly  directed  to  the 
following  few  points.  Among  the  more  important  constituents  of  the 
sputum  are  :  water,  salts,  cells,  mucin,  serum  albumen  (coagulated 
and  uncoagulated),  serum  globulin,  ferments,  excreted  medicaments,  and 
bacteria.    These  vary  within  very  wide  limits  under  different  conditions. 

To  the  chemical  constituents  of  the  sputum  little  attention  has 
been  paid  in  practical  medicine;  the  following  recent  observations, 
however,  are  of  considerable  interest,  and  may  prove  of  great  service  in 
the  diagnosis  of  obscure  lung  conditions. 

Falk  and  Tedesco  {Wien.  med.  Woch.,  igog,  xxii,  g54)  have  noted  the 
fact  that  salicylic  acid  present  in  the  blood  appears  in  inflammatory 
exudates  in  the  lung,  but  is  not  excreted  by  the  bronchial  mucosa ;  the 
application  of  the  following  test  will  therefore  assist  in  differentiating 
disease  processes  hmited  to  the  bronchial  mucosa  from  those  which 
have  extended  to  the  lung. 

Thirty  grains  of  sodium  salicylate  are  given  by  the  mouth  and  the 
sputum  collected  during  the  ensuing  twelve  to  eighteen  hours.  It  is 
slightly  acidified  with  acetic  acid  and  shaken  thoroughly  with  five 
times  its  volume  of  absolute  alcohol.  The  mucus  and  albumen  are 
precipitated  in  coarse  flocculi  and  removed  by  filtration.  The  clear 
filtrate,  which  contains  all  the  sahcylate  acid,  if  any  be  present,  is 
rendered  slightly  alkaline,  and  evaporated  to  dryness  over  a  water 
bath ;  the  residue  is  dissolved  in  water,  slightly  acidified,  and  sugar  of 
lead  added  till  no  more  precipitate  forms  :  this  latter  is  removed  by 
filtration  and  washed  with  water,  the  washings  being  added  to  the  acid 
filtrate,  which  is  then  extracted  with  ether.  The  ethereal  extract  is 
evaporated  to  dryness,  the  residue  dissolved  in  lo  c.c.  of  water,  and 
I  c.c.  of  10  per  cent,  aqueous  solution  of  ferric  chloride  is  added. 
The  formation  of  a  violet  colour  indicates  the  presence  of  salicylic 
acid.     Patients  suffering  from  catarrhal  bronchitis,  bronchitis,  emphy- 


12  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

sema,  bronchial  asthma,  purulent  bronchitis,  and  bronchiectasis  all  gave 
negative  results,  whereas  cases  of  lobar  pneumonia  reacted  strongly. 

The  reaction  gradually  lessens  until  the  crisis  is  reached,  when  it 
rapidly  disappears,  and  varies  in  intensity  roughly  with  the  extent  of 
lung  affected.  In  phthisis  the  results  varied  ;  a  positive  result  was 
always  obtained,  but  the  intensity  was  not  proportional  to  the  clinical 
severity  or  the  extent  of  the  process.  Generally,  however,  acute  cases 
gave  a  stronger  reaction  than  chronic.  Falk  and  Tedesco  hold  that  a 
repeatedly  negative  result  is  strong  evidence  that  the  process  is  limited 
to  the  bronchial  mucosa,  and  is  therefore  exclusive  of  pneumonia  or 
pulmonary  phthisis.    ■ 

Lesieur  and  Prirez  {Paris  Medical,  191 1,  vol.  iv,  p.  29)  have  investi- 
gated the  sputum  voided  in  various  conditions  for  albumen  content  : 
5  c.c.  of  sputum  are  taken;  to  this  20  c.c.  of  normal  salt  solution  and 
five  or  six  drops  of  acetic  acid  are  added.  The  mixture  is  well  shaken  and 
filtered  ;  the  filtrate  is  then  tested  for  albumen  by  boiling  or  with  nitric 
acid.  If  the  reaction  by  boiling  be  doubtful  the  addition  of  a  further 
20  c.c.  of  salt  solution  and  fresh  boiling  will  sometimes  give  a  positive 
result.  Lesieur  and  Prirez  found  that  of  cases  without  physical  signs 
which  subsequently  proved  to  be  tuberculous  75  per  cent,  gave  a 
positive  reaction  ;  that  all  cases  with  tubercle  bacilli  in  the  sputum  were 
positive  ;  that  in  miliary  tuberculosis  and  pleurisy  the  result  was  not 
constant  ;  that  cases  of  acute  lobar  pneumonia  reacted,  and  that  when 
the  reaction  persisted  into  convalescence  a  new  focus  or  a  complication 
was  indicated.  Acute  broncho-pneumonia  and  acute  pulmonary 
oedema  were  also  positive.  On  the  other  hand,  in  acute  bronchitis  it 
was  usually  negative,  in  chronic  bronchitis  and  in  emphysema  always 
so.     In  cardio-renal  cases  a  positive  reaction  was  often  seen. 

In  840  observations  by  various  authors  the  reaction  was  given  in 
100  per  cent,  of  cases  where  tubercle  bacilli  were  present,  in  82  per 
cent,  of  cases  which  were  probably  tuberculous  and  in  37  per  cent, 
of  non-tuberculous  cases.  As  with  the  salicylic  acid  test,  it  would  thus 
seem  that  a  positive  reaction  indicates  a  pulmonary  origin  of  the  exu- 
date and  excludes  a  bronchial  source,  and  that  the  more  marked  and 
more  constant  the  result  the  greater  the  likelihood  of  phthisis  or 
pneumonia. 

(2)  Staining  methods  for  cells  and  their  derivatives. — The  most  complete 
account  of  the  constituents  of  the  sputum  other  than  bacterial  and  how 
these  vary  in  health  and  disease  is  to  be  found  in  Etude  Histochimique 
et  Cytologique  des  Crachats,  by  Israels  de  Jong,  from  which  I  have 
taken  many  of  the  following  particulars.  The  staining  method  which 
de  Jong  found  most  generally  useful  is  as  follows  :  A  thin  film  of  the 
secretion  is  prepared  and  allowed  to  dry  without  the  application  of 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


13 


heat  ;  it  is  then  fixed  for  two  or  three  seconds  in  i  per  cent,  aqueous 
solution  of  chromic  acid,  washed  well  under  the  tap,  stained  for  three 
minutes  in  undiluted  polychrome  methylene-blue  of  Unna,  differentiated 
with  go  per  cent,  alcohol,  washed  well  with  v^^ater,  dried  by  the  appli- 
cation of  gentle  heat  and  examined  by  the  aid  of  artificial  light. 
Owing  to  the  metachromatic  properties  of  this  stain,  red  corpuscles, 
mucin,  epithelial  cells,  leucocytes  and  their  granules  are  coloured 
differently.  The  red  cells  appear  green,  mucin  reddish,  the  nuclei  of 
the  epithelial  cells  characteristically  a  deep  violet,  almost  black,  their 
cytoplasm  a  light  violet  to  lilac,  the  nuclei  of  the  leucocytes  a  deep 
violet  to  black,  their  cytoplasm  a  light  violet,  the  granules  of  mast- 
cells  reddish ;  those  of  the  eosinophiles  are  unstained,  yet  clearly 
visible  on  account  of  their  refractility  and  double  contour. 

Unna's  polychrome  methylene-blue  is  a  by  no  means  easy  stain  to 
manage,  and  requires  considerable  practice  in  order  to  obtain  satis- 
factory results.  As  an  alternative,  still  better  as  a  supplementary 
method,  one  of  the  various  modifications  of  Romanowsky's  stain, 
preferably  Leishman's,  may  be  employed.  Here  let  me  just  mention 
that  if  one  makes  up  the  liquid  stain  for  himself  the  following  points 
must  be  observed  :  (i)  Use  only  Grubler's  stain  and  the  purest  methyl 
alcohol ;  (2)  dissolve  o"4  grm.  of  the  former  in  200  c.c.  of  the  latter, 
place  in  a  well-corked  flask,  shake  daily  for  a  fortnight,  and  filter 
thoroughly  when  transferring  to  the  stain  bottle  ;  at  least  a  fortnight's 
maturation  of  the  solution  is  requisite. 

The  technique  for  Leishman's  stain  is  as  follows  :  Films  should 
be  made  upon  well-cleaned  slides,  spread  thinly  and  allowed  to 
dry  in  the  air  without  the  application  of  heat.  The  slide  is  covered 
with  the  stain,  which  is  allowed  to  remain  for  three  minutes  in 
hot  weather,  for  five  in  cold;  the  preparation  is  then  flooded  with 
distilled  water,  which  is  well  mixed  with  the  stain  by  means  of  a 
pipette.  The  mixture  is  allowed  to  remain  for  fifteen  minutes,  then 
poured  away  and  the  slide  plunged  into  plenty  of  distilled  water ;  in 
this  the  preparation  is  agitated  until  no  more  stain  comes  away  ;  it  is 
then  washed  with  fresh  distilled  water,  lightly  blotted  between  filter- 
paper  and  dried  by  warming  gently.  Examination  is  best  made  without 
the  use  of  a  cover-slip.  Bacteria  are  stained  blue,  cell  nuclei  dark  blue, 
cytoplasm  lilac  or  pink  according  to  the  cell,  basophile  granules  violet, 
acidophile  granules  red,  red  blood-corpuscles  red,  mucin  a  dirty  blue. 

The  cells  of  the  pharyngeal  mucosa  (Plate  I,  fig.  I)  are  very  large 
cells,  irregularly  polygonal  in  shape,  with  a  large  oval  nucleus  placed 
either  centrally  or  near  the  periphery.  With  Unna's  stain  the 
nucleus  of  the  undegenerated  cell  takes  on  a  deep  violet  colour, 
the  cytoplasm  a  feeble  blue-violet.    With  Leishman's  stain  the  nucleus 


14  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

is  deep  blue,  the  protoplasm  reddish-violet.  These  cells  are  fre- 
quently seen  crowded  with  bacteria,  especially  when  beginning  to 
degenerate  (as  in  Fig.  I).  The  degenerative  process  proceeds  rapidly, 
the  cell  then  having  a  greater  affinity  for  acid  than  for  basic 
stains,  so  that  the  cytoplasm  may  appear  a  bright  red  with  Leishman's 
stain. 

The  cells  of  the  bronchial  mucosa  (Plate  I,  figs.  \la  and  116). — 
The  bronchial  mucosa  consists  of  several  layers  of  stratified  cylin- 
drical epithelium  with  a  superficial  ciliated  layer.  Normal  bronchial 
cells  are  rare  in  sputum  except  in  cases  of  severe  early  trancheitis  or  in 
acute  asthma ;  in  these  instances  violent  fits  of  coughing  may  lead  to 
the  tearing  off  of  small  portions  of  the  mucosa  ;  even  here  a  certain 
amount  of  degeneration  has  as  a  rule  set  in.  The  ciliated  superficial 
layer  consists  of  a  cylindrical  cell  with  large  oval  nucleus.  The  outer 
end  of  the  cell  is  flat  and  covered  with  cilias  ;  the  other  end  is  drawn 
out,  sometimes  bifid,  and  insinuates  itself  beneath  the  neighbouring 
cell  or  cells  (Fig.  11a).  The  deeper  cells  are  polyhedral  or  shaped  like 
a  truncated  cone  with  large  nuclei. 

By  Unna's  stain  the  nucleus  of  the  normal  cells  stains  violet  and 
uniformly,  the  cytoplasm  bluish.  The  normal  cell,  as  said  before, 
is  very  rarely  seen  ;  usually  degeneration  has  already  set  in.  The  nucleus 
then  appears  reticulated,  swollen,  and  occupying  perhaps  two  thirds  of 
the  cell ;  later  it  may  be  drawn  out  into  a  long  network  protruding 
from  the  cell  (Fig.  116)  ;  still  later  the  cytoplasm  may  entirely  disappear 
and  the  nuclear  reticulum  be  drawn  out  into  long  strands,  which  have 
often  been  mistaken  for  fibrin,  and  may  include  polynuclear  cells  in  their 
network — an  appearance  often  seen  in  acute  and  chronic  bronchitis. 
The  cytoplasm  of  the  degenerating  cell  with  Unna's  stain  appears  of  a 
lilac  colour,  the  nucleus,  unlike  that  of  most  other  cells,  stains  reddish 
with  a  slight  violet  tinge  like  mucin. 

Leishman's  stain  is  but  ill  adapted  for  showing  the  bronchial 
cells  in  their  various  stages  of  degeneration  ;  with  it  the  nuclear  reti- 
culum appears  lilac  to  blue,  according  to  the  amount  of  washing  to 
which  the  preparation  is  subjected. 

The  cells  of  the  pulmonary  alveoli  (Plate  I,  figs.  Ill  and  IV). — 
These,  unlike  the  bronchial  cells,  are  frequently  to  be  seen  in  the 
sputum  in  their  more  or  less  normal  condition,  as  well  as  in  their 
degenerative  forms. 

The  normal  alveolar  epithelium  consists  of  a  thick  layer  of  large 
plaques  without  nuclei  bound  together  by  a  kind  of  cement ;  between 
these  lamellar  cells  are  small  dark  protoplasmic  areas  with  well-defined 
nuclei.  The  layer  of  unnucleated  cells  covers  the  capillary  network, 
whilst  the  nucleated  protoplasm  occupies  the  mesh  of  the  blood-vessels. 


PLAT£    1. 


j^^2S^ 


Diagrammatic  representations  of  constituents  of  sputum  (after  Israels  de  Jong).  Fig.  I.  Pharyn- 
geal cell  with  bacteria.  Fig.  II  a.  Cell  of  superficial  layer  of  bronchial  mucosa.  Fig.  II  b. 
Bronchial  cell  undergoing  degeneration  with  extrusion  of  nucleus.  Fig.  III.  Small  pul- 
monary cells.  Fig.  IVa.  Macrophagic  pulmonary  cell.  Fig.  W  b.  Ditto  with  pigment- 
granules.  Fig.  V.  Sputum  of  pneumonia  at  about  eighth  day  :  (a)  Polynuclears  ;  (6)  Sero- 
albuminous  exudate;  (c)  Hyaline  mucus:  {d)  Pulmonary  alveolar  cells;  {e)  Mucinous 
reticulum  derived  from  cell  nuclei,  and  containing  in  its  mesh  polynuclear  cells  and  bacteria. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  I  5 

The  precise  origin  of  the  unnucleated  plaques  is  unknown,  but  they  are 
probably  derived  from  the  small  nucleated  cells. 

In  the  sputum  these  cells  may  appear  in  the  following  forms :  {a) 
As  the  above  small  nucleated  cell  (Figs.  Ill  and  V^);  {b)  as  a  large 
macrophagic  cell  often  laden  with  pigment  (Figs.  IVa  and  IV  h) ; 
(c)  as  a  degenerated  reticulum.  The  small  nucleated  alveolar 
cell  somewhat  resembles  the  mononuclear  cells  of  the  blood,  but 
differs  from  them  in  certain  particulars.  The  nucleus  is  round  or 
oval,  occupying  the  centre  of  the  cell  and  filling  about  two- 
thirds  of  it.  The  cell  itself  is  small,  round,  or  slightly  oval,  the 
cytoplasm  apparently  granular.  With  Unna's  blue  the  nucleus  stains 
a  dark  violet,  the  cytoplasm  a  much  lighter  violet,  and  showing 
innumerable  tiny  basic  granules ;  this  cell  is  very  common  in  the 
sputum  of  pneumonia,  broncho-pneumonia,  pulmonary  congestion, 
softening  phthisis,  and  capillary  bronchitis  ;  it  is  rare  in  acute 
bronchitis  and  in  emphysema  with  bronchitis.  If  they  make  their 
appearance  during  the  course  of  a  bronchitis  they  indicate  capillary 
extension,  pulmonary  congestion,  or  an  area  of  pneumonia  ;  these  cells 
are  distinguished  from  the  mononuclears  of  the  blood,  which  probably 
appear  but  very  rarely  in  pulmonary  exudates,  by  their  nucleus  being 
more  oval,  more  compact,  and  staining  too  deeply,  by  the  protoplasm 
being  more  abundant,  and  with  greater  affinity  for  stains. 

The  endothelial  macrophages  (Figs.  IVa  and  YVh)  are  large  cells 
with  an  excentric  nucleus ;  sometimes  they  are  bi-  or  even  tri-nucleated ; 
sometimes  the  cytoplasm  is  abundant,  vacuolated,  and  stains  feebly 
except  at  the  periphery  ;  sometimes  it  is  quite  scanty  and  stains  deeply. 
Between  this  cell  and  the  small  alveolar  cell  there  are  all  gradations,  and 
the  former  is  probably  only  a  specialised  form  or  derivative  of  the  latter. 

The  macrophages  are  often  laden  with  particles  of  pigment,  derived 
either  from  the  air,  when  they  are  deep  brown  or  black,  or  from  the 
blood-pigment,  when  they  are  golden  (Fig.  IV  6).  They  are  found  in 
such  conditions  as  resolving  pneumonia  and  broncho-pneumonia,  in 
bronchitis  with  pulmonary  congestion,  and  in  pulmonary  congestion 
due  to  granular  kidney. 

As  with  the  bronchial  cell,  so  with  the  pulmonary  in  an  advanced 
stage  of  degeneration,  all  that  may  remain  of  the  cell  is  a  reticulum 
derived  from  the  nucleus,  and  having  the  staining  reactions  of  mucin. 
With  Unna's  blue  they  stain  red  and  more  deeply  than  the  bronchial 
reticula,  from  which  they  also  differ  in  being  more  compact,  less 
drawn  out  and  less  fine,  and  in  frequently  containing  bacteria  and 
leucocytes  in  their  mesh  (Fig.  V^).  With  stains  such  as  Leishman's  this 
reticulum  preserves  its  basis  affinity  much  more  strongly  than  does  that 
derived  from  the  bronchial  cell ;    sometimes  the  reticulum  appears  to 


1 6  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

preserve  the  outline  of  the  cell ;  sometimes  those  derived  from  several 
cells  appear  to  unite  to  form  a  larger  network. 

Blood-cells  in  the  sputum. — For  the  study  of  these  elements  no  stain 
is  so  well  adapted  as  that  of  Leishman  ;  their  appearances  are  too 
well  known  to  need  description.  It  will  suffice  to  mention  (i)  that 
red  cells  are  found  in  any  form  of  acute  pulmonary  congestion,  and 
that  their  appearance  in  the  sputum  of  bronchitis  is  indicative  of 
alveolar  extension;  (2)  that  degenerative  changes  occur,  the  nuclei 
of  polymorphonuclears  undergoing  extrusion,  lying  as  a  long  thread 
attached  to  the  cell  or  by  the  side  of  it,  and  staining  the  reddish  colour 
characteristic  of  mucin,  whilst  the  granules,  especially  of  the  coarsely 
granular  eosinophiles,  are  frequently  shed  from  the  cells  as  if  by  a 
violent  explosion.  This  is  especially  well  seen  in  sputum  from  a  case 
of  acute  asthma,  in  which  disease  only,  tuberculosis  excepted,  do 
coarsely  granular  eosinophiles  appear  in  considerable  numbers  in  the 
sputum. 

The  mucin  of  the  sputum  (Plate  I,  fig.  Vc). — So  much  attention 
has  been  drawn  to  the  degeneration  of  the  nuclei  of  the  bronchial 
and  pulmonary  cells  as  a  source  of  mucin  that  the  question  may 
well  be  asked.  Is  this  the  source  of  all  the  mucin  of  the  sputum  ? 
The  answer  is,  Certainly  not ;  the  great  bulk  of  sputum  is  composed 
of  mucus  secreted  by  the  special  mucous  glands,  the  product  apparently 
of  their  nuclear  activity,  but  differing  from  that  previously  described  by 
its  hyaline  non-reticular  structure  (Fig.  Vc).  These  glands  are  most 
numerous  in  the  trachea,  less  so  in  the  bronchi ;  as  the  bronchi  approach 
the  lung  the  mucous  glands  become  fewer  and  fewer  until  they  cease 
to  exist  in  the  smaller  bronchioles. 

It  may  appear  somewhat  superfluous  further  to  labour  the  point 
that  much  of  what  has  been  described  in  the  past  and  is  regarded  at 
the  present  as  fibrin  in  sputum  is  not  fibrin,  but  mucin,  but  the  point  is 
a  very  important  one,  for  fibrin  is  the  coagulated  form  of  the  sero- 
albuminous  exudate  from  lung-tissue  proper,  the  significance  of  which 
has  already  been  referred  to  under  the  salol  and  albumen  tests. 

The  sero-albuminous  constituents  of  sputum  (Plate  I,  fig.  Yb). — As 
has  been  already  stated,  mucin  stains  reddish  to  reddish-violet  with 
Unna's  blue,  violet  to  blue  with  Leishman's  stain,  and  very  feebly 
blue  with  Weigert's  stain ;  fibrin,  on  the  other  hand,  stains  blue-grey 
to  blue-green  with  Unna's  blue,  red  with  Leishman's  stain,  and  deep 
blue  by  Weigert's  method.  The  fibrinous  reticulum  is  composed  of 
straight  fibrils  crossing  each  other  in  every  direction,  vs^hile  the  mucous 
reticulum  is  wavy,  and  composed  of  fibrils  which  anastomose  in  various 
curves. 

If   the    sputum    of   such    conditions  as   acute    pulmonary    cedema. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  1 7 

phthisis,  or  early  pneumonia  be  stained,  by  the  above  methods  numerous 
rounded  masses  which  often  seem  to  coalesce  are  seen  stained  violet- 
blue  or  blue-grey.  These  droplets  vary  in  size  and  shape  (Fig.  Vb)  :  the 
smallest  have  about  thrice  the  diameter  of  a  red  blood-cell  and  are  round ; 
the  largerare  oval ;  larger  still  they  are  irregular  and  lobulated  as  if  by  the 
coalescence  of  several  droplets — in  acute  pulmonary  oedema  practically 
the  whole  of  the  exudate  consist  of  this  body  ;  in  pneumonia  they 
appear  during  the  stage  of  hepatisation  and  disappear  with  the  redux 
crepitation  ;  they  may  constitute  the  whole  groundwork  of  the  prepara- 
tion as  if  the  droplets  had  all  run  together. 

Inasmuch  as  precisely  similar  effects  are  obtained  by  suitably 
stained  serum,  pleural  exudate,  ascitic  fluid  or  albuminous  urine,  there 
is  little  doubt  that  this  substance  is  derived  from  the  blood,  and  like 
the  albuminoid  constituents  of  the  blood,  possesses  a  somewhat 
complex  constitution. 

We  now  pass  on  to  consideration  of  the  staining  methods  suitable 
for  demonstrating  the  bacterial  flora  of  the  respiratory  passages  in 
smear  preparations  and  in  culture  films.  The  payment  of  attention  to 
the  following  points  will  be  found  distinctly  advantageous  : 

(i)  Smears  and  films  alike  should  be  made,  not  upon  cover-slips, 
but  upon  new,  well-cleaned  slides  ;  the  gain  in  ease  of  manipulation  is 
considerable. 

(2)  Due  heed  should  be  paid  to  the  selection  of  the  specimen  ;  it  is 
little  use  selecting  a  piece  of  laryngeal  or  tracheal  mucus  when  the 
desire  is  to  ascertain  the  pulmonary  conditions  as  regards  bacterial 
contents.  Sometimes  it  is  necessary  to  prepare  multiple  smears,  for 
even  to  the  naked  eye  the  specimen  supplied  may  not  present  a  homo- 
geneous appearance.  Thin  films  have  a  distinct  advantage  over  thick 
ones  except  when  we  are  dealing  with  nasal  mucus,  and  it  is  not 
desirable  to  cover  more  than,  say,  the  middle  third  of  the  slide  with 
material. 

(3)  Stains  which  are  liable  to  sedimentation  should  be  carefully 
filtered  immediately  prior  to  use. 

(4)  A  good  lens  is  a  prime  necessity  and  a  movable  stage  a  decided 
advantage  ;  it  should  be  made  an  invariable  rule  to  use  either  natural 
or  artificial   illumination,   not   sometimes  one,   sometimes  the  other. 

(5)  The  gravity  of  an  infection  is  not  necessarily  proportional  to  the 
number  of  bacteria  present  in  a  smear,  nor  in  mixed  infections  is  the 
relative  import  of  the  several  invaders  proportional  to  the  respective 
numbers ;  due  care  should  therefore  be  taken  in  searching  the  slide 
lest  amidst  the  many  the  few  be  missed. 

In  the  study  of  the  bacteria  of  the  respiratory  tract  skill  in  the 
technique   of  the    following    staining   methods  is   essential :    Gram's  ; 


1 8  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

Ziehl  -  Neelsen's  with  Spengler's  modifications,  Leishman's  or 
Giemsa's  ;  Muir's  (for  capsules)  ;  Van  Ermengen's  or  Muir-Pitfield's 
(forflagella).  Satisfactory  results  with  each  of  these  should  be  secured 
by  adopting  the  following  procedures  : 

Gram's  method. — Materials  required:  Saturated  alcoholic  solution 
of  gentian  violet  (5  grms.  in  100  c.c.  of  90  per  cent,  alcohol),  Lugol's 
solution  of  iodine  (iodine  i  grm.,  potassium  iodide  3  grm.,  distilled 
water  300  c.c.)  ;  saturated  aqueous  solution  of  aniline  oil,  absolute 
alcohol,  I  per  cent,  aqueous  solution  of  neutral  red. 

Procedure. — A  thin  uniform  smear  on  a  clean  slide  is  allowed  to  dry  in 
the  air,  fixed  by  passage  three  or  four  times  through  the  Bunsen  flame, 
while  warm  flooded  with  the  aqueous  solution  of  aniline  oil  which  is 
filtered  at  the  time ;  the  alcoholic  gentian  violet  is  then  allowed  to  drop 
upon  the  slide,  one  drop  at  each  quarter  fnch  ;  this  ensures  proper 
mixture  of  stain  and  mordaunt,  which  is  allowed  to  remain  for  between 
two  and  three  minutes  ;  it  is  then  poured  off  and  the  slide  washed  under 
the  tap.  The  preparation  is  now  covered  with  Lugol's  iodine  solution 
for  fifteen  seconds,  washed  under  the  tap,  and  flooded  with  absolute 
alcohol,  which  is  replaced  by  fresh  alcohol  after  two  or  three  minutes. 
After  a  like  interval  the  smear  is  again  washed  with  water,  held  slightly 
aslant,  and  absolute  alcohol  dropped  upon  it ;  when  no  more  stain 
appears  in  the  washings  decoloration  is  complete.  Wash  again  with 
water,  pour  on  the  slide  the  aqueous  solution  of  neutral  red,  leaving  it 
on  for  sixty  seconds  in  cold  weather,  for  forty-five  seconds  in  hot,  wash 
with  water,  dry  gently  between  folds  of  filtered  paper,  and  then  over 
the  Bunsen  flame.  Those  bacteria  which  retain  a  violet  colour  are 
said  to  be  Gram-positive,  those  which  lose  it  and  assume  a  light  red 
from  the  neutral  red  are  said  to  be  Gram-negative.  Most  varieties  of 
bacteria  are  definitely  either  Gram  +  or  Gram  —  ,  but  a  few,  such  as 
Micrococcus  paratetragemis  and  some  strains  of  B.  coli  occurring  in  urine 
are  not  definitely  either  one  or  the  other  and  may  be  called  Gram  ±. 
In  a  few  other  instances  certain  strains  of  a  bacterium  retain  Gram's 
stain  more  or  less  definitely,  while  those  which  do  not  yet  fail 
to  assume  the  neutral  red  ;  some  strains  of  the  tubercle  bacillus  are  in 
point. 

Ziehl-Neelsen's  method. — Materials  required  :  Carbol-fuchsin  {basic 
fuchsin  I  grm.,  carbolic  acid  crystals  5  grm.  ;  dissolve  in  100  c.c. 
distilled  water  and  add  10  c.c.  absolute  alcohol),  15  per  cent,  aqueous 
solution  of  nitric  acid,  absolute  alcohol,  i  per  cent,  aqueous  solution  of 
toluedene  blue. 

Procedure. — Fix  film  by  passage  or  three  four  times  through  Bunsen 
flame,  place  vertically  in  staining  dish  (to  prevent  deposition  of  stain), 
filter  the  carbol-fuchsin  which  has  been  heated  to  about  40°  C.  into  the 


THE    BACTERIAL    DISEASES    OF    RESITRATIOX.  19 

dish  till  slide  is  quite  immersed ;  place  the  whole  in  incubator  for  five 
to  ten  minutes,  take  out  the  slide  and  wash  well  in  water,  immerse  in 
15  per  cent,  nitric  acid  for  fifteen  to  twenty  seconds,  wash  in  water, 
again  place  in  acid,  wash  with  water,  then  with  absolute  alcohol  till  no 
more  stain  is  discharged,  again  with  water  ;  finally  counter-stain  for 
one  to  two  minutes  with  i  per  cent,  aqueous  toluedene  blue,  wash 
well  under  the  tap,  blot  lightly  and  dry.  The  bacteria,  such  as  the 
tubercle,  smegma,  lepra,  and  Timothy-grass  bacilli  which  retain  the 
carbol-fuchsin  stain  after  this  procedure  are  said  to  be  acid-fast.  In 
as  much  as  the  presence  of  scanty  numbers  of  tubercle  bacilli  in  a 
specimen  of  sputum  may  be  detected  only  with  considerable  difficulty 
when  this  procedure  is  strictly  followed,  various  modifications  of 
Ziehl-Neelsen's  method  have  been  devised.  Some  of  these  are  con- 
cerned with  the  actual  staining  processes,  others  merely  with  the 
preliminary  treatment  of  the  sputum ;  under  the  former  head  fall 
Spengler's  methods  I  and  II,  under  the  latter  the  antiformin  and 
pepsin  methods. 

Spenghrs  method  jVo.  I. — The  smear  is  allowed  to  dry  in  the  air. 
then  covered  for  thirtv  to  sixty  seconds  with  i  per  cent,  aqueous  solu- 
tion of  caustic  soda :  this  dissolves  the  mucus,  but  certainly  does  not 
seem  to  displace  the  bacilli;  the  caustic  soda  is  poured  off";  of  what 
remains  adherent  to  the  slide  as  much  as  possible  is  removed  b}- touch- 
ing with  the  edge  of  filter-paper,  the  smear  is  then  dried  best  in  the 
incubator  or  very  cautiously  over  the  Bunsen  flame,  covered  with 
Loffler's  methylene  blue  for  two  to  three  minutes,  washed  well  with 
water,  stained  as  before  in  warm  carbol  fuchsin,  washed  well  with 
water,  decolorised  and  counterstained  by  flooding  the  slide  for  thirty 
to  fortv-five  seconds  with  Loffler's  methylene  blue  to  which  five  to  ten 
drops  of  15  per  cent,  aqueous  solution  of  nitric  acid  have  been  added. 
The  slide  is  then  washed  well  with  water,  blotted  lightly  and  dried 
carefully. 

Spengler's  method  Xo.  II. — Allow  a  thin  smear  to  dry  in  the  air,  stain 
as  before  at  a  temperature  of  35"-40"  C.  in  carbol  fuchsin,  without 
washing  flood  the  slide  with  a  mixture  of  equal  parts  of  absolute  alcohol 
and  of  either  Esbach's  solution  or  of  a  saturated  aqueous  solution  of 
picric  acid,  pour  oft"  after  about  flve  seconds,  wash  for  a  few  seconds 
with  15  per  cent,  nitric  acid,  flood  with  picric  acid-alcohol;  when  the 
smear  is  of  a  hght  yellow  colour,  wash  with  distilled  water,  dry 
carefully,  wash  with  60  per  cent,  alcohol,  then  for  a  few  seconds  with 
15  per  cent,  nitric  acid,  and  again  with  60  per  cent,  alcohol.  Finally 
contrast  stain  with  the  picric  acid-alcohol  until  the  smear  is  well 
coloured,  wash  with  distilled  water,  and  dry  carefully.  This  method 
is  somewhat  tedious,  but  verv  reliable,  and  by  it  forms  which  Spengler 


20  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

has  named  "  splitter"  are  well  demonstrated;  these  frequently  appear 
as  minute  red  granules,  and  are  probably  infant  bacilli.  By  it  I  have 
frequently  been  enabled  to  detect  tubercle  bacilli  in  sputum  which  other 
methods  have  entirely  failed  to  reveal. 

The  antifovmin  method  has  been  devised  not  only  for  the  concen- 
tration of  the  tubercle  bacilli  in  a  specimen  of  sputum,  so  that  very 
scanty  numbers  may  be  detected  with  ease,  but  also  for  the  obtaining 
of  pure  cultures  of  the  tubercle  bacilli  direct  from  the  sputum;  it  per- 
forms both  ends  with  conspicuous  success.  Antiformin  is  a  mixture  of 
equal  parts  of  a  15  per  cent,  aqueous  solution  of  caustic  soda  and  the 
liquor  sodse  chlorinatas  of  the  B.P.  The  procedure  is  as  follows  :  5  c.c. 
of  the  sputum  are  placed  in  a  sterilised  test-tube  supplied  with  a  well- 
fitting  rubber  cork;  to  this  5  per  cent,  of  a  30  per  cent,  aqueous  solution 
of  antiformin  are  added,  the  tube  is  stoppered,  well  shaken  till  all  the 
sputum  is  dissolved  and  a  homogeneous  mixture  secured.  It  is  then 
placed  in  the  incubator  at  37°  C.  for  one  hour.  The  liquid  is  distri- 
buted into  two  sterile  centrifuge  tubes  and  centrifuged  at  a  high  speed 
for  five  minutes,  the  supernatant  liquid  is  pipetted  off,  to  the  sediment 
in  each  tube  5  c.c.  sterilised  distilled  water  are  added,  and  thorough 
centrifugalisation  performed ;  this  procedure  is  twice  repeated.  The 
final  sediment  is  employed  for  the  insemination  of  tubes  of  Dorset's 
egg  medium,  and  for  the  preparation  of  smears  which  are  stained 
according  to  one  or  other  of  the  preceding  methods — best  by  Spengler 
No.  II.  Personally,  I  add  5  c.c.  of  the  mixture  after  incubation  to  one 
centrifuge  tube,  and  2  or  3  c.c.  only  to  the  other,  making  the  volume 
up  to  5  c.c.  with  absolute  alcohol.  The  latter  tube  has  a  distinctive 
mark,  and  subsequent  washings  of  the  sediment  are  carried  out  with  40 
per  cent,  alcohol.  The  addition  of  the  alcohol  lowers  the  specific 
gravity  of  the  liquid,  and  facilitates  the  deposit  of  the  tubercle  bacilli; 
this  tube  cannot  be  used  for  culture  purposes,  but  only  for  the  pre- 
paration of  smears. 

The  pepsin  and  trypsin  methods  depend  upon  the  digestion  of  the 
sputum  with  acid  pepsin  or  alkaline  trypsin  prior  to  centrifugalisation. 
In  opposition  to  the  view  of  their  advocates  I  do  not  think  they  have 
any  advantage  whatever  over  the  antiformin  method,  which,  in  my 
hands  as  well  as  those  of  others,  has  proved  most  reliable  and  valuable. 

Leishuuin's  method  has  been  already  described  on  p.  13,  and  serves 
well  to  display  the  spirochastes,  vibrios  and  spirilla  of  the  mouth; 
]f  more  intense  staining  be  desired,  a  10  per  cent,  aqueous  solution  of 
carbol-fuchsin  may  be  applied  for  forty-five  seconds,  followed  by  thorough 
washing  in  running  water.  Even  in  this  dilution  carbol-fuchsin  is  both 
an  intense  and  diffuse  stain ;  it  must  therefore  be  remembered  that  the 
bacteria  as  seen  under  the  microscope  will  appear  unduly  large.     The 


ERRATUM. 

Page  20,  line    13,   instead  of  "to  this   5    per  cent,  of  a   30 

per  cent,   aqueous  solution  " 
read  "  to   this   5    c.c.   of  a  30  per  cent,  aqueous  solution  " 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  2  1 

Stains  which  give  the  truest  pictures  are  Loffler's  methylene  and  carbol- 
methylene  blue,  but  unfortunately  they  are  not  of  general  utility;  their 
use  is  too  well  known  to  require  description. 

Muir's  method  for  capsules  in  my  hands  has  proved  as  good  as  any. 
An  advantage  is  its  simphcity ;  a  disadvantage  the  fact  that  the  capsules 
thereby  are  stained  a  weak  blue  or  sometimes  not  at  all,  in  which  case, 
however,  they  stand  out  as  a  clear  zone  around  the  bacillus.  The 
following  is  the  composition  of  the  fixative  and  mordant :  Saturated 
aqueous  solution  of  corrosive  sublimate  2  c.c,  20  per  cent,  aqueous 
solution  of  tannic  acid  2  c.c,  saturated  aqueous  solution  of  potash  alum 
5  c.c;  mix.  The  film  is  dried  in  the  air,  then  fixed  in  the  above  for 
two  minutes,  washed  in  water,  then  in  methylated  spirit,  and  again  in 
water.  Stain  in  warm  carbol-fuchsin  for  three  to  five  minutes,  wash 
in  water,  place  in  mordant  for  three  minutes,  wash  in  water.  Stain 
for  three  minutes  in  a  saturated  aqueous  solution  of  methylene  blue, 
differentiate  with  methylated  spirit— a  process  requiring  considerable 
care — wash  with  water  and  dry  carefully.  Bacteria  which  form  capsules 
as  a  rule  do  so  only  in  the  body,  occasionally  when  cultured  in  milk  or 
fluid  media  containing  body  fluids,  rarely  when  allowed  to  incubate  in 
the  secretions  in  which  they  are  voided  ;  it  thus  follows  that  in  warm 
weather  when,  say,  pneumococci  may  multiply  in  the  sputum  during 
transit,  only  some  of  the  forms  will  be  seen  to  be  capsulated  in  smears 
prepared  from  such  a  specimen.  (Fig.  i  shows  bacillus  of  Friedlander 
capsules  stained  by  this  method.) 

Van  Ermengens  method  for  flagella. — Inasmuch  as  this  is  a  precipita- 
tion process  and  not  a  true  staining  one,  it  necessarily  results  in  an 
undue  enlargement  of  the  stained  elements  ;  on  the  other  hand,  it  is 
much  the  most  reliable  method.  To  secure  good  results  it  is  absolutely 
essential  that  due  regard  be  paid  to  the  following  points : 

(i)  New  slides  which  have  been  thoroughly  cleansed  must  alone  be 
used  for  the  preparation  of  the  specimen. 

(2)  Young  cultures  grown  on  solid  and  not  in  liquid  media  should 
alone  be  employed. 

(3)  A  small  portion  of  the  growth  should  be  emulsified  very  gently 
in  distilled  water  contained  in  a  clean  watch-glass,  a  drop  of  the  emul- 
sion taken  up  with  the  platinum  loop  and  carefully  led  over  the  centre 
of  the  slide  rather  than  rubbed  upon  it ;  the  film  should  be  allowed  to 
dry  in  the  air  and  not  heated  ;  if  too  thick  it  should  be  discarded. 

(4)  Plenty  of  sensitising  fluid  should  be  available,  and  no  portion 
of  it  should  be  used  a  second  time  even  for  the  same  preparation. 
Three  solutions  are  required  :  (a)  Fixing  solution  composed  of  2  per 
cent,  solution  of  osmic  acid  in  distilled  water  i  part,  20  per  cent,  solu- 
tion  of  tannin  in  distilled  water  2  parts;    {b)  sensitising  solution,  o"5 


2  2  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

per  cent,  silver  nitrate  solution  in  distilled  water  ;  (c)  reducing  solution 
composed  of  gallic  acid  5  grm.,  tannin  3  grm.,  fused  potassium  acetate 
10  grm.,  dissolved  in  350  cc.  distilled  water  and  carefully  filtered. 

The  procedure  is  as  follows  :  The  air-dried  film  is  placed  in  a  bath 
of  the  fixing  solution  at  a  temperature  of  about  50°  C.  for  ten  minutes, 
washed  thoroughly  with  distilled  water,  then  with  absolute  alcohol  for 
four  to  five  minutes,  and  again  with  distilled  water.  It  is  placed 
in  the  sensitising  solution  for  thirty  to  forty  seconds,  and  without 
washing  transferred  to  the  reducing  solution  until  it  turns  yellow- 
brown  :  this  usually  takes  between  one  and  two  minutes.  The 
specimen  is  then  transferred  to  a  bath  of  fresh  sensitising  solution 
until  it  turns  brown-black  ;  this  usually  takes  only  a  few  seconds.  It 
is  washed  with  plenty  of  distilled  water,  very  carefully  "dried  with 
filter-paper,  then  over  the  Bunsen  flame.  This  method  is  particularly 
useful  for  the  demonstration  of  spirochaetes,  spirilla  and  vibrios,  but, 
as  said  before,  it  must  be  remembered  that  the  micro-organisms  will 
appear  unduly  large.     (Fig.  2  shows  B.  siibtilis  with  flagella.) 


PLATE    II. 


Fig.  I. — Bacillus  of  Friedlander  (capsules) 
and  B.  inflnenzce  in  sputum.  (Muir's 
method.)      x    looo. 


Fig. 


-B.  xiibtilis,  with  flr 
X    2O0O. 


sUa. 


.-^ 


Fig.  4 — Streptothrix  from  case  of  bron- 
chial catarrh.  Film  from  agar  culture 
stained  by  Gram's  method.       x    lOOO. 


Fig.  3. — B.  tuberculosis. 
Antiformin  method. 
Six  weeks'  growth. 


Fig.  5. — Streptothrix. 
Agar  cul  t  u  re. 
(Slightly  reduced.) 


CHAPTER    III. 

CULTURAL  METHODS  FOR  INVESTIGATING  THE  BACTE- 
RIOLOGY OF  THE  RESPIRATORY  TRACT:  DESCRIP- 
TION OF  THE  BACTERIA  WHICH  MAY  BE  PRESENT. 

To  enter  into  a  full  description  of  all  the  cultural  methods 
applicable  to  this  study  would  be  quite  beyond  the  scope  of  this  small 
book  ;  there  are,  however,  certain  methods  which  are  indispensable, 
and  one  or  two  others  which  I  have  devised  myself  for  special  pur- 
poses, and  these  may  be  here  considered.  Two  preliminary  points 
require  emphasis :  (i)  that  plate  cultures  have  a  great  advantage  over 
tube-slopes  for  isolation  purposes.  The  surface  is  much  greater  and 
more  accessible,  while  naked-eye  appearances  are  more  easily  studied. 
(2)  One  medium  is  above  all  others  indispensable  ;  if  cultures  upon 
this  be  not  made,  then  the  investigation  is  vitiated  and  worthless  from 
the  outset.  I  refer  to  blood-agar,  and  for  its  preparation  human  blood 
and  not  that  of  animals  should  be  employed.  For  two  years  my 
assistant  and  self  have  furnished  all  the  blood  we  have  required  and 
never  have  we  had  a  contaminated  plate.  The  procedure  we  have 
adopted  is  as  follows  :  12-15  c.c.  of  sterilised  5  per  cent,  sodium 
citrate  are  placed  in  a  sterile  tube ;  a  capillary  pipette  is  made  from  a 
piece  of  glass  tubing  -f^  in.  in  diameter,  sterilised  and  fitted  with  a 
strong  rubber  teat.  The  tips  of  the  middle  fingers  of  the  left  hand 
are  sterilised  with  20  per  cent,  lysol,  which  is  washed  off  with  absolute 
alcohol.  The  finger  tip  is  flexed,  and  with  a  surgical  needle  one  or 
two  punctures  are  made  in  the  middle  of  the  terminal  joint.  The 
blood  should  flow  freely,  and  is  taken  up  by  means  of  the  pipette,  into 
which  a  little  of  the  citrate  solution  has  been  already  taken.  About 
2  c.c.  of  blood  should  be  furnished  by  the  one  finger  and  are  sufficient 
for  one  tube  of  citrate  solution.  To  10  c.c.  of  2  per  cent,  melted 
agar  {+  10  Eyre's  scale)  at  60°  C.  about  1*5  c.c.  of  the  blood  citrate 
solution  are  added,  and  well  mixed  with  the  agar  by  the  rotation  of 
the  inclined  tube  between  the  palms.  The  mixture  is  then  poured 
quickly  into  a  sterilised  Petri  dish  of  3f  in.  diameter.  No  lump  of 
unmelted  agar  should  disturb  the  surface  of  the  plate.     About  eight 


24  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

plates  can  thus  be  prepared  from  one  finger  tip.  Any  effort  to  conserve 
the  agar  is  to  be  strongly  deprecated,  for  frequently  plates  require  three 
days'  incubation,  at  the  end  of  which  time  the  unduly  thin  plate  will 
have  so  dried  in  the  incubator  as  to  be  ill-adapted  for  bacterial  growth  ; 
the  above  quantity,  lo  c.c,  is  the  least  which  should  be  used  for  a 
plate  of  3I  in.  in  diameter. 

Other  media  which  are  necessary  for  the  more  or  less  complete 
study  of  this  question  are  : 

Agar  (+  10  Eyre's  scale). 

Serum-agar  (blood  serum  one  part,  2  per  cent,  agar  three  parts). 

Acid-blood  agar  (blood  agar  made  as  above  except  that  to  the  agar 
[+10  Eyre's  scale]  i  per  cent,  hydrochloric  acid  has  been  added). 

Dorset's  egg  medium  (take  fresh  hen's  egg,  sterilise  shell,  break, 
mix  yolk  and  white  thoroughly,  add  distilled  water  to  25  per  cent., 
pour  into  sterile  test-tubes  one  inch  in  diameter,  avoiding  all  bubbles, 
slant,  heat  in  inspissator  at  85°  C.  for  half  an  hour  on  each  of  three 
successive  days). 

Peptone  broth — 

Peptone  water  (0*5  per  cent,  peptone  solution). 

Sugar  media  (o"5  per  cent,  peptone  water  to  which  2  per  cent,  of 
the  various  sugars  has  been  added  ;  of  these  it  is  well  to  have  dextrose, 
levulose,  saccharose,  lactose,  maltose,  galactose,  mannite,  dextrin,  sor- 
bite, dulcite,  inulin). 

Acid-blood-peptone  broth, /.^.  10  c.c.  peptone  broth,  i  c.c.  blood 
citrate  mixture,  to  which  have  been  added  o"5  per  cent,  of  lactic  acid 
and  o"5  per  cent,  potassium  tartrate  (for  mouth  organisms). 

Special  media  such  as  MacConkey's  are  at  times  useful,  and  a 
contrivance  for  anaerobic  incubation  may  be  necessary. 

The  preliminary  examination  of  stained  srhears  will  enable  the 
decision  to  be  made  as  to  what  media  are  to  be  employed,  the  use  of  a 
blood  agar  plate  being  obligatory :  it  will  also  indicate  how  much 
material  is  to  be  employed  for  insemination  purposes.  As  a  rule  the 
amount  of  secretion  taken  up  by  a  platinum  loop  one  tenth  of  an  inch 
in  diameter  will  suffice ;  with  this  the  blood  agar  plate  is  lightly  streaked, 
the  last  stroke  being  made  parallel  to,  but  at  the  margin  of  the  plate 
opposite  to  the  first.  In  this  way  discrete  colonies  are  certain  to 
be  secured;  if  they  develop  too  thickly  on  the  first  few  streaks  they  will 
be  sufficiently  separate  on  some  of  the  subsequent  ones.  The  plate  is 
incubated  at  ^y°  C.  for  twenty-four  hours  and  examined  by  direct 
observation  and  by  means  of  stained  films.  It  is  then  returned  to  the 
incubator  for  another  twenty-four  hours,  for  some  bacteria  such  as  B. 
influenza,  B.  Bordet-Gengou,  may  have  developed  but  slightly  by  the 
end  of  the  first  day,  but  will  be  easily  seen  by  the  end  of  the  second. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  2$ 

Subcultures  may  be  made  upon  plates  or  slopes.  Upon  blood-agar 
the  following  varieties  of  bacteria  will  freely  grow :  Staphylococci, 
streptococci,  pneumococci,  B.  infliienzcB,  B.  Bordet-Gengou,  B.  Koch- 
Weeks,  B.  diphthericE,  B.  Hoffmanii,  B.  xerosis,  B.  septus,  M.  catarrhalis, 
M.  paratetragenus,  M.  tetragenus,  B.  of  Friedlander,  B.  ^rofcHs,  B.pyo- 
cyaneus,  B.  coli,  and  B.  typhosus;  in  fact  all  the  pathogenic  bacteria  of 
the  respiratory  tract  with  the  exception  of  the  tubercle  bacillus,  lepra 
bacillus,  streptothrix  actinomycosis,  Spirochceta  pallida,  and  the  vibrios, 
streptothrices,  spirochgetes,  and  fusiform  bacilli  associated  with  pyor- 
rhoea alveolaris — the  artificial  cultivation  of  all  these  is  not  yet  possible; 
to  those  which  can  be  cultured  the  following  methods  are  applicable : 

The  tubercle  bacillus. — The  sputum  having  been  treated  by  the 
antiformin  method  as  already  outlined,  several  loopfuls  of  the  final 
sediment  are  streaked  upon  the  surface  of  one  or  two  tubes  of  the 
above-mentioned  Dorset's  egg-medium  :  after  twenty-four  to  forty- 
eight  hours'  incubation  at  37°  C.  the  cotton  plug  is  flamed,  pushed 
down  the  tube,  and  the  orifice  fitted  with  a  rubber  cap  in  order  to 
prevent  undue  evaporation  of  moisture.  After  two  to  three  weeks' 
incubation,  pin-head  colonies  of  the  tubercle  bacillus  will  be  visible  in 
the  great  majority  of  cases  in  which  this  organism  is  present  (Fig.  3). 

The  streptothrix  actinomycosis. — By  far  the  best  medium  for  the 
growth  of  this  organism  is  the  hydrochloric  acid  blood-agar.  After 
forty-eight  to  seventy-two  hours'  incubation  there  will  be  a  strongly  acid 
odour  like  acetic  acid,  the  colour  of  the  medium  will  be  turned  brownish 
instead  of  blood-pink  (from  the  formation,  I  beheve,  of  methhasmoglo- 
bin),  and  small  colonies,  white  in  colour,  horny  in  consistency,  and 
crinkled  on  the  surface  will  be  found  strongly  adherent  to  the  surface ; 
after  another  day  or  two's  incubation  they  seem  to  have  actually  eaten 
their  way  into  the  agar. 

The  vibrios,  streptothrices  and  spirochsetes  of  the  mouth  and  sputum 
are  peculiarly  difficult  to  grow;  the  most  useful  medium  is  the  blood 
peptone  broth  with  lactic  acid  and  potassium  tartrate  above  referred 
to.  With  this  I  have  at  times  secured  abundant  growth,  sometimes 
after  anaerobic,  sometimes  after  aerobic  incubation,  sometimes  after  only 
six  hours'  incubation,  sometimes  after  forty-eight  hours.  The  products 
of  growth  are  intensely  toxic.  Very  occasionally  pure  growths  can  be 
obtained  upon  agar  or  blood  agar  from  this  blood  broth  (see  Figs.  4  and  5) . 

When  pure  cultures  of  each  of  the  bacteria  seen  in  the  smears,  or 
of  as  many  of  them  as  can  be  induced  to  grow,  have  been  obtained,  the 
study  of  their  behaviour  on  the  special  differentiating  media  which 
appear  to  be  indicated  may  be  pursued.  The  characteristics,  morpho- 
logical and  cultural,  which  I  have  found  of  the  greatest  value  for 
differentiation  purposes  will  be  referred  to  briefly  in  the  following  section. 


26  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

The  Tubercle  bacillus  may  very  rarely  require  to  be  differentiated  from 
the  lepra  bacillus,  the  smegma  bacillus,  and  the  B.  Phlei  (Timothy- 
grass  bacillus),  and  the  Mycobacterium  lacticola;  of  these  the  first 
only  is  of  importance  in  diseases  of  the  respiratory  tract  inasmuch  as 
40  per  cent,  of  lepers  are  said  to  die  from  tuberculosis.  The  presence 
of  vast  numbers  of  acid-fast  bacilli  within  the  typical  leprous  cell  is 
suggestive  of  leprosy,  but  fails  to  disprove  the  possible  simultaneous 
presence  of  the  tubercle  bacillus.  Lepra  bacilli  do  not  grow,  except  in 
subcultures,  commonly  or  with  any  freedom  upon  Dorset's  egg-medium, 
hence  the  appearance  of  copious  growth  in  three  to  four  weeks  thereon 
is  almost  proof  positive  of  the  presence  of  tubercle  bacilli.  If  no 
growth  be  obtained,  the  inoculation  of  a  rabbit  and  a  guinea-pig  with 
some  of  the  materies  morbi  may  be  necessary  to  confirm  the  presence 
of  the  tubercle  bacillus.  For  recent  work  upon  the  cultivation  of  the 
lepra  bacillus  the  reader  must  be  referred  to  the  writings  of  Clegg 
{Philippine  Journal  of  Science,  December,  igog,  p.  403)  ;  Williams  (sup- 
plement, Indian  Med.  Gazette,  May,  igii  ;  Brit.  Med.  Journ.,  December 
i6th,  igii,  p.  158),  Rost,  Twort,  and  Bayon  {Brit.  Med.  Journ., 
November  nth,  igii,  p.  i26g).  Once  the  lepra  bacillus  has  been 
obtained  in  'pure  culture  it  is  said  by  Clegg  to  grow  readily  upon 
any  of  the  ordinary  laboratory  media,  growth  upon  glycerine-agar 
or  Dorset's  egg-medium  being  so  profuse  in  three  days  that  the 
whole  surface  may  be  covered  with  a  heaped-up  moist,  creamy 
growth,  which  can  be  readily  detached  and  emulsifies  easily  in  salt 
solution. 

The  main  problem  which  confronts  us  in  regard  to  the  B.  tuberculosis 
is  the  determination  of  the  type  to  which  the  given  specimen  belongs  ; 
is  it  of  human  or  of  bovine  origin  ?  The  utility  of  Spengler's  staining 
methods  for  this  end  I  am  unable  to  confirm.  Growth  upon  Dorset's 
egg-medium  affords  no  indication.  Agglutination  tests  have  no  value. 
Inoculation  tests  have  a  distinct  value,  but  are  difficult  to  carry  out, 
and  facilities  for  their  performance  not  easy  to  obtain.  The  growth  in 
broth  and  determination  of  the  acid  or  alkali  formed  at  weekly  intervals 
(Theobald  Smith's  method)  is  the  best  available  test,  but  is,  again,  by 
no  means  easy  to  perform.  In  the  case  of  the  human  strain  the 
medium  will  remain  acid  throughout,  whereas  in  the  case  of  the  bovine 
strain,  after  a  preliminary  rise  in  the  acidity  an  alkaline  reaction  will 
finally  appear.  In  short,  to  any  but  the  specialised  laboratory  worker 
upon  the  tubercle  bacillus  differentiation  is  a  practical  impossibility. 
The  reflection  that  in  a  certain  small  percentage  of  cases  mixed  infection 
by  both  types  exists  will  not  excite  unduly  the  enthusiasm  of  the 
already  busy  man.  How  the  difficulty  can  be  obviated  I  will  indicate 
later  when  I  come  to  section  IV  (8). 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  2  7 

The  Streptothrix  actinomycosis. — This  term  is  a  generic  one  com- 
prising many  members.  That  transmission  of  infection  by  the  Actino- 
myces bovis  to  man  from  horses  or  oxen  does  occur  is  certain,  whilst 
infection  without  such  an  intermediary  direct  from  barley  is  also 
possible.  Streptothrices  of  various  kinds  are  exceedingly  common  in 
the  infected  foci  of  pyorrhoea  alveolaris,  and  to  their  astiological  signiii- 
■cance  but  scant  attention  has  been  directed.  Upon  three  occasions 
lately  I  have  isolated  a  streptothrix  from  the  sputum  in  cases  of  acute 
bronchial  catarrh  (Figs.  4  and  5),  while  an  organism  somew'hat  similar 
to  mine  but  grouped  as  a  leptothrix  has  been  described  by  McDonald 
(Jonrn.  Path,  and  Bad.,  igo8,  p.  447)  as  the  probable  cause  of  a  number 
of  cases  of  cerebro-spinal  meningitis. 

The  relationship  of  these  various  organisms  to  the  common 
.Streptothrix  actinomycosis  bovis  is  undetermined.  Streptothricial 
■disease  of  the  lung  in  man  is  probably  much  commoner  than  is 
supposed  to  be  the  case,  the  greater  proportion  of  instances  being 
missed  for  these  reasons  :  (i)  The  organism  is  difficult  to  cultivate ; 
•(2)  the  typical  yellow  granule  if  detected  in  the  sputum  may  be  mis- 
taken for  a  food-particle  or  for  a  fragment  of  a  plug  discharged  from 
a  follicular  tonsillitis  and  examination  be  neglected.  These  plugs  are 
by  no  means  uncommon  in  sputum  from  such  cases,  and  on  exami- 
nation may  be  found  to  contain  numerous  streptothricial  filaments — 
the  clubs  and  spherical  bodies  (gonidia)  and  arrangement  of  the 
colonies  typical  of  the  true  ray  fungus  will  however  be  lacking,  while 
cultural  tests  will  assist  in  the  discrimination.  The  discharge  of 
yellow  granules  in  the  sputum  from  a  case  presenting  obscure 
pulmonary  symptoms  should  always  awake  suspicion  of  an  actinomy- 
•cotic  or  streptothricial  infection. 

The  Spirochceta  pallida  is  hardly  likely  to  make  its  appearance  in 
the  sputum  or  nasal  discharge ;  on  the  other  hand,  its  presence  may 
be  anticipated  in  smears  prepared  from  scrapings  taken  from  ulcerated 
surfaces  of  the  respiratory  tract,  and  it  will  be  necessary  to  dis- 
criminate it  from  the  common  Spinchata  refringens  of  the  mouth. 
Space  forbids  me  entering  into  this  question,  and  the  reader  must  be 
referred  to  any  one  of  the  numerous  monographs  which  have  appeared 
■of  late  upon  this  subject. 

The  staphylococcus  {albus,  aureus,  citreus,  candicans)  is  too  well 
known  an  organism  to  require  any  detailed  description.  It  is  the 
commonest  inhabitant  of  the  upper  respiratory  tract  under  ordinary 
■conditions ;  in  the  pathological  state  it  tends,  if  anything,  to  be  dis- 
placed by  the  new  invaders  ;  to  estimate  its  significance  in  disease  is, 
therefore,  no  easy  matter.  Its  role  in  pulmonary  phthisis  will  be  referred 
to  fully  in  Section  IV  (8)   {a).     In  diphtheria  of  the  throat  it  is  fre- 


2  8  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

quently  present,  but  the  fact  that  spraying  with  Hving  cultures  of  the 
Staphylococcus  atcreus  has  been  strongly  advocated  by  several  observers 
as  a  most  useful  means  of  destroying  such  diphtheria  bacilli  as  persist 
during  convalescence  may  be  taken  to  indicate  that  it  exercises  any- 
thing but  a  prejudicial  action  in  this  condition.  As  secondary  infection 
in  lupus,  syphilis,  leprosy  and  tuberculosis  of  the  upper  passages  it  is 
well  recognised  as  playing  an  important  part. 

In  some  cases  of  rhinitis  caseosa  which  I  have  examined  it  would 
appear  to  have  possessed  an  setiological  significance,  but  in  the  various 
catarrhal  infections  of  the  respiratory  tract  it  apparently  is  not  con- 
cerned excepting  in  cases  of  empyemata  of  the  accessory  spaces,  and 
here  but  rarely. 

The  pigment  formation  is  a  variable  property,  and  it  is  by  no  means 
certain  that  the  aureus  is  incapable  of  transformation  into  the  albus. 
The  term  "  citreus"  is  for  all  practical  purposes  a  perfectly  useless  one 
and  is  best  abandoned.  The  Staphylococcus,  or  better-termed  Micrococcus 
candicans,  is  probably  a  distinct  and  always  non-pathogenic  variety, 
possibly  identical  with  the  Micrococcus  urece  ;  colonies  on  gelatin  or 
agar  are  round,  moistly  shining,  porcelain-white  and  slightly  elevated. 
Microscopically  they  are  about  V2  \x  in  diameter,  i.e.  about  half  as 
large  again  as  the  ordinary  staphylococcus.  Usually  they  present  a 
dividing  line  in  the  centre,  and  are  Gram-positive. 

The  streptococcus  is  an  exceedingly  important  group  in  catarrhal 
diseases  of  the  respiratory  tract ;  its  importance  is  far  beyond  that 
which  would  be  gathered  from  any  publication  upon  the  subject.  The 
numerous  attempts  which  have  been  made  to  divide  and  classify  the 
various  members  of  the  group  have  failed  utterly,  na}^  more,  they  are 
intrinsically  misleading.  To  call  a  certain  strain  a  Streptococcus  sali- 
varius  or  Streptococctis  nnicosus  was  synonymous,  until  very  recently,  with 
attributing  it  with  total  lack  of  pathogenicity  ;  nothing  could  be  further 
from  the  truth,  and  I  would  suggest,  except  in  purely  academic  dis- 
cussion, the  abandonment  of  all  such  terms  as  "  salivarius,''  "  mucosus," 
"  fcBcalis,"  and  "  viridans."  At  the  same  time  I  must  admit  that  the 
study  of  many  scores  of  different  strains  has  left  me  unable  to  suggest 
a  better  classification.  The  discrimination  between  the  pneumo- 
coccus  and  some  strains  of  mouth  streptococci  is  by  no  means  easy. 
It  is  stated  that  incubation  with  pure  ox-bile  for  thirty  minutes  will 
result  in  the  lysis  of  all  varieties  of  the  streptococcus  but  the  pneumo- 
coccus  and  the  so-called  Streptococcus  salivarius. 

It  is  also  stated  that  the  Streptococcus  salivarius  may  possess  capsules 
like  the  pneumococcus.  The  sugar  reactions  are  so  variable  as  to  be 
almost  devoid  of  value,  and  in  the  pathogenicity  tests  I  am  a  total 
disbeliever,  being  unable  to  forget  an  experience  when  on  the  staff 


PLATE    III. 


Uu;;*>6->'^ 


Fig.   7. — Streptococcus   maximi 
(asthma).      x    looo. 


Fig.   10. — Streptococcus  longus 
(asthma).      x    1000. 


Fig.  6.  —  Streptococcus 
maximus  (blood  agar). 
Natural  size. 


P'lG.  8.  —  Streptococcus 
large  from  mouth  (agar). 
Natural  size. 


Fig.  9. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  29 

of  the  Royal  E3''e  Hospital.  We  had  an  epidemic  of  conjunctivitis  of 
extreme  severity  and  of  extremely  rapid  course — in  eighteen  to  twenty- 
four  hours  a  complete  hypopyon  with  ulceration  of  the  cornea  usually 
ensued.  The  lanceolate,  Gram-positive,  capsulated  diplococci  were  tested 
on  rabbits  and  guinea-pigs,  stated  to  be  non-pathogenic  and  therefore 
not  pneumococci — could  anything  be  more  absurd  ?  I  do  not  for 
one  moment  wish  to  decry  the  value  of  close  scientific  observation, 
but  so  far  its  results  as  regards  the  streptococcus  group  have  been 
most  unsatisfactory.  There  is  one  variety  of  this  organism  appear- 
ing to  possess  constant  characteristics,  which  is  of  the  utmost 
importance  in  certain  pathological  conditions  of  the  respiratory 
tract,  and  which,  probably  owing  to  the  fact  that  it  is  highly 
hasmophilic  and  refuses  to  grow  on  agar  alone,  appears  to  have  escaped 
recognition ;  for  reasons  which  will  appear  I  have  called  it  Strepto- 
coccus Jiiaxiuius.  Frequently  in  the  sputum  from  cases  of  bronchitis 
and  asthma  there  may  be  seen  long  chains  of  a  very  large  strepto- 
coccus, the  individual  members  of  which  are  about  double  the  size 
of  the  ordinary  Streptococcus  pyogenes  longus  from  an  abscess.  By 
Gram's  method  they  stain  diffusely,  decolorising  with  a  certain 
amount  of  ease,  so  that  some  members  of  the  chain  may  be  quite 
Gram  +  ,  others  Gram±,  and  yet  others  Gram  —  .  Fig.  7  is  an  excellent 
reproduction  by  Dr.  Ralph  Vincent  of  this  organism ;  it  will  be  noticed 
that  here  and  there  is  an  element  which  has  failed  to  retain  the  Gram 
stain.  The  chains  may  be  composed  of  many  individuals,  20,  40,  100, 
or  even  200,  the  average  being  40  to  60.  Occasionally  there  may  be 
obtained  from  the  mouth  a  strain  which  microscopically  closely 
resembles  this  one,  but  culturally  is  entirely  distinct ;  in  broth  it  forms 
a  compact  sediment,  which  on  being  shaken  up  speedily  settles  again 
to  the  bottom,  grows  readily  on  agar  (Fig.  8),  on  blood  agar  forms 
discrete  white  colonies  no  larger  than  a  small  pin's  head  (Fig.  9), 
but  readily  visible  by  reflected  or  transmitted  light.  In  the  case  of 
Streptococcus  maximus  peptone  broth  remains  clear,  a  slim}'  deposit 
forming,  which  on  being  shaken  up  shows  its  viscid  nature.  On 
agar  it  very  rarely  shows  any  growth  at  all,  on  blood  agar  it  grows 
with  the  utmost  ease;  on  plates  sown  not  too  thickly  colonies  may 
attain  a  diameter  of  well  over  |  in. ;  they  are  round,  almost  colour- 
less, dew-droppy  in  appearance,  slimy,  and  tend  to  coalesce.  On 
blood  agar  slopes  the  colonies  are  difficult  to  see  except  with  oblique 
illumination.  Dr.  Vincent  has  had  great  difficulty  in  securing  a 
photograph  of  the  growth,  but  finally,  by  deft  manipulation  of  the 
illumination,  secured  the  picture  seen  in  Fig.  6.  An  excellent  idea  of 
the  nature  of  the  growth  may  be  formed  if  it  be  remembered  that  the 
colonies  are  perfectly  colourless  when  viewed  by  natural  reflected  light ; 


30  THE    BACTERIAL    DISEASES    OE    RESPIRATION. 

the  size  of  the  colonies  and  their  tendency  to  coalesce  are  well  shown. 
The  above  characteristics  suffice  amply  to  identify  this  Streptococcus 
maximiis,  and  to  differentiate  it  from  the  large  streptococcus  of  the 
mouth.  In  other  cases,  especially  of  asthma  with  scanty  viscid  mucus, 
there  is  frequently. to  be  seen  a  totally  different  streptococcus;  both  in 
smears  and  cultures  it  forms  chains  of  exceeding  length  which  may 
traverse  half  a  dozen  fields  of  the  microscope  (see  Fig,  lo).  In  size 
the  individual  members  of  the  chain  show  no  variation  from  the 
ordinary  Streptococcus  pyogenes  longus,  and  I  have  discovered  no  method 
of  differentiating  between  the  two. 

For  the  rest  I  can  merely  say  that  we  may  have  streptococci  pos- 
sessing only  two,  six,  eight,  a  dozen  or  twenty  members  in  a  chain, 
streptococci  possessing  lOO  or  200  in  a  chain  ;  we  may  have  streptococci 
which  on  blood  agar  turn  the  blood  green  or  turn  it  brown,  hsemolyse 
or  do  not  hsemolyse,  which  form  colonies  which  are  dry  or  moist,  white 
or  almost  colourless,  which  in  broth  form  flocculi,  a  uniform  haze,  or 
dense  deposit ;  all  these  characteristics  mean  little  or  nothing  in  the 
present  state  of  our  knowledge.  The  fact  remains  that  each  and  every 
one  may  under  suitable  conditions  become  pathogenic  to  the  human 
subject  in  a  greater  or  less  degree,  and  there  is  no  laboratory  test  which 
will  settle  the  question  whether  in  the  particular  case  under  review 
they  are  concerned  in  the  process  of  disease  or  are  not  concerned  in 
it.  It  is  experience  and  a  general  review  of  the  whole  bacterio- 
logical flora  which  will  guide  aright,  and  the  results  of  vaccine  treat- 
ment which  will  confirm  or  refute  the  accuracy  of  the  deductions. 
For  the  purposes  of  this  paper  the  streptococci,  then,  will  be  divided 
merely  into  these  groups — maximns,  longus,  and  brevis. 

The  pneumococcus,  as  seen  in  stained  preparations  of  the  secretions,  is 
typically  a  Gram-positive,  capsulated,  lanceolate  coccus,  usually  occurring 
in  pairs,  occasionally  in  short  chains  of  four  to  six  members  (Fig.  11). 
The  best  medium  for  its  cultivation  is  human  blood-agar,  upon  which  it 
appears  in  twenty-four  hours  as  minute,  round,  transparent,  dew-drop- 
like colonies,  thicker  at  the  periphery  than  in  the  centre  so  that  they 
present  a  ring-like  appearance  ;  usually  they  hsemolyse  the  medium  so 
that  there  is  a  clear  area  around  each  colony;  sometimes  they  also  appear 
to  turn  it  green,  a  sign,  some  observers  maintain,  of  their  high  virulence  ; 
sometimes  again  they  appear  to  turn  the  medium  brown  (Fig.  12). 

Stained  films  of  such  a  growth  show  Gram-positive  lanceolated 
cocci,  usually  arranged  in  pairs,  sometimes  in  short  chains'of  four,  six, 
or  eight  members  (Fig.  13). 

In  broth  a  slight  uniform  turbidity  is  produced,  the  addition  of  a 
little  blood  to  the  broth  increasing  the  amount  of  growth  ;  a  slight 
dust-like  deposit  may  settle  to  the  bottom  of  the  tube.     If  a  hanging 


PLATE   IV. 


Fig.  II. — Pnemnococci  in 
sputum.  (Gram's  stain.) 
X    looo. 


S^  >:Si^, 


Fig.    13. —  Pneumocorcus. 
(Gram's  stain)     x    lOOO 


Fig.    12. — Piieumococcus.     (Blood 
agar)      Natural  size. 


Fig.  14. — B.  influenzce      (Carbol 
fuchsin.)      X    looo. 


Fig.  15. — Koch-Weeks'  B.    (Carbol- 
fuchsin.)      X    looo. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  3  I 

drop   or    stained   film    be    examined    numerous    chains   of    four,    six, 
or  eight  individuals  will  be  observed. 

The  fact  that  growth  does  not  occur  on  gelatine  or  agar  at  room 
temperatures  assists  to  differentiate  the  pneumococcus  from  some  strains 
of  the  short  mouth  streptococcus  ;  the  distinction,  however,  is  not  an 
absolute  one,  for  some  of  these  latter  also  fail  to  grow  under  like 
conditions. 

I  have  already  referred  to  the  failure  of  inoculation  tests  to  prove 
or  negative  the  fact  that  a  given  organism  is  a  pneumococcus.  With 
those  who  hold  that  some  strains  of  the  mouth  streptococcus  are 
capsulated  and  behave  like  the  pneumococcus  when  incubated  with 
ox-bile  I  am  unable  to  agree,  and  consider  that  they  were  dealing  with 
true  pneumococci  of  low  virulence,  and  that  it  is  best  to  regard  all 
capsulated.  Gram-positive,  lanceolate  diplococci  which  give  the  charac- 
teristic colonies  on  blood-agar  as  true  pneumococci,  no  matter  what 
their  fermenting  powers  or  pathogenic  properties  in  animals. 

The  Bacilhts  influenza,  B.  of  Koch- Weeks,  and  B.  of  Bordet-Gengou 
are  very  closely  allied  organisms,  nay,  further,  the  former  two  are 
probably  identical,  although  the  fact  that  with  the  acute  conjunctivitis 
due  to  the  Koch-Weeks'  bacillus  it  is  very  rare  to  find  a  concurrent 
respiratory  catarrh  is  rather  against  this  view ;  microscopically  they  are 
indistinguishable  (Figs.  14  and  15). 

The  Bacillus  inflnenzce  and  B.  Koch-Weeks  only  grow  in  or  on  media 
containing  blood  or  haemoglobin,  viz.  blood  broth  or  blood-agar.  If  a 
thin  layer  of  blood-broth  be  inseminated  and  incubated  at  ^y°  C.  for 
twenty-four  hours,  delicate  white  flocculi  are  to  be  seen  ;  on  blood-agar 
after  twenty-four  hours'  incubation  at  37°  C.  pin-point  colonies^  round, 
perfectly  colourless  and  moist,  are  formed ;  after  forty-eight  hours 
these  may  attain  a  diameter  of  y^  in.  and  by  reflected  light  are  per- 
fectly colourless,  by  transmitted  light  grey  to  whitish. 

Microscopically  they  consist  of  very  narrow  short  rods,  0*4  ju  broad, 
i'2-i'5  ju  long,  which  fail  to  retain  the  stain  by  Gram's  method,  but 
take  up  the  neutral  red.  Weak  carbol  fuchsin  shows  them  up  most 
clearly,  but  from  its  intense  and  diffuse  action  causes  them  to  appear 
unduly  large  (Figs.  14  and  15).  Sometimes  they  appear  in  pairs, 
sometimes  short  filaments  are  formed,  this  characteristic  being  peculiar 
to  certain  strains  of  unusual  luxuriance  of  growth  which  are,  perhaps, 
pseudo  rather  than  true  influenza  bacilli.  In  the  secretion  they  often 
appear  inside  the  cells,  and  yet  more  frequently  are  aggregated  around 
the  pulmonary  or  polynuclear  cells.  The  Bacillus  Bordet-Gengou  (of 
whooping-cough)  differs  from  the  B.  influenzce  in  being  slightly  larger, 
ovoid,  more  regular  in  size  and  in  exhibiting  polar  staining.  In 
cultural  properties  it  also  differs,  growing  best  upon  glycerine-potato- 


32  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

blood-agar,  and  on  serum  agar,  upon  which  latter  medium  the  influenza 
bacillus  grows  with  difficulty.  Upon  the  former  medium  after  twenty- 
four  hours'  incubation  at  ^y°  pin-point  colonies  may  appear  ;  these  will 
be  B.  influenzcB.  After  forty-eight  to  seventy-two  hours  much  larger  and 
more  vigorous  colonies  which  do  not  haemolyse  the  blood  medium  may 
be  seen.  These  are  colonies  of  the  bacillus  of  Bordet-Gengou.  In  sub- 
cultures they  form  a  dense,  grey,  glistening,  and  very  vigorous  growth 
of  discrete  colonies.  The  tendency  of  the  B.  influenzc^,  on  the  other 
hand,  is  to  die  out  rapidly  when  sub-cultured.  The  addition  of  various 
bacterial  toxins,  as  of  the  B.  coli,  pneumococcus  or  staphylococcus  to 
the  blood  agar  will  frequently  result  in  an  extraordinary  profuse 
growth  of  the  B.  inflnenzcB  {vide  Vaccine  Therapy,  3rd  edition,  pp.  174, 
175).  It  may  be  noted  that  in  the  majority  of  cases  of  whooping- 
cough  the  B.  infliienzcB  appears  to  be  present  along  with  the  Bordet's 
bacillus.  The  significance  of  this  fact  in  the  treatment  of  whooping- 
cough  by  means  of  vaccine  is  obvious. 

The  Bacillus  diphtheric^  (Klebs-Loefiler),  B.  of.  Hoffmann,  B.  xerosis 
and  B.  septus  constitute  the  group  of  so-called  diphtheroid  bacilli. 
While  it  is  true  that  the  first  of  these  is  usually  associated  with  the 
formation  of  a  membrane,  be  it  in  the  throat,  larynx,  nose  or  eye,  it  yet 
happens  that  it  may  be  resident  in  the  throat  in  the  absence  of  any 
membrane,  either  persisting  for  months  after  the  subsidence  of  all  acute 
symptoms  of  a  diphtheritic  attack,  or  maintaining  a  constant  sapro- 
phytic existence  there,  at  no  time  causing  any  symptoms,  but  being  a 
continual  potential  source  of  danger  either  to  its  host  or  to  others  to 
whom  it  may  be  conveyed  :   such  individuals  are  known  as  "  carriers." 

The  bacillus  of  Hoffmann  is  a  frequent  cause  of  epidemic  sore 
thro.at,  not  so  frequent,  however,  I  believe,  as  it  is  held  to  be  by  many 
observers,  who  may  possibly  have  confused  it  with  the  Bacillus  septus. 
So  far  as  I  know  Hoffmann's  bacillus  does  not  invade  the  nose,  and 
would  not  appear  ever  to  cause  an  acute  rhinitis. 

The  Bacillus  xerosis  is  believed  to  be  non-pathogenic ;  whether  it 
is  entirely  devoid  of  pathogenicity  is  in  my  opinion  debatable,  but 
whether  it  be  or  not,  its  pathogenicity  is  certainly  very  low.  It  is 
commonly  found  associated  with  other  bacteria  in  chronic  inflammatory 
conditions  of  the  ocular  and  urethral  mucous  membranes.  It  might 
therefore  be  anticipated  that  it  would  frequently  be  found  resident  on 
the  nasal  mucosa,  especially  in  those  suffering  from  conjunctival 
inflammation ;  such,  however,  I  have  not  found  to  be  the  case ; 
the  only  diphtheroid  commonly  found  in  the  nose  is  the  Bacillus 
septus. 

The  Bacillus  septus  is  associated  with  catarrhal  affections  of  the  nose, 
naso-pharynx,  and  throat.     Only  once  have  I  found  it  in  the  sputum 


PLATE    V. 


►^  f 


Fro    1 6. — B.  septus  and  M. 
catarrhalis.       x  lOOO. 


%5> 


V 


Fig.  23. — Diphtheria  bacillus,        Fig.  2i. — 5.  Hoffmann,  twenty- 
twentv-four  hours.    (Gram.)         four  hours.     (Gram.)     x  looo. 


Fig.  17. — B.  diphthericB, 

twenty-four  hours. 

Natural  size. 


Fig.  18. — B.  xerosis,  twenty - 
four  hours.     Natural  size. 


Fig.  19. — B.  septus 
twenty-four  hours. 
Natural  size. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  3  3 

from  a  case  of  bronchial  catarrh  (see  Fig.  i6,  a  smear  of  the  sputum  of 
this  case ;  the  deeply-stained  cocci  are  M.  catarrhalis,  the  faintly 
stained  rods  B.  septus).  This  was  a  long-standing  infection,  the 
expectoration  was  profuse  and  very  purulent-looking,  although  almost 
free  from  cells  and  consisting  almost  exclusively  of  mucus  and  bac- 
teria and  was  most  offensive  ;  if  incubated  for  twenty-four  hours  the 
odour  was  overpowering,  with  a  suggestion  of  impure  petrol  about  it. 
This  case  will  be  more  fully  referred  to  in  a  subsequent  number. 
Upon  two  other  occasions  I  have  isolated  from  the  sputum  a 
diphtheroid  bacillus  which  was  not  a  member  of  any  of  these  four 
groups.  On  agar  and  blood  agar  it  formed  round,  discrete,  moist,  oily 
colonies,  the  colour  of  which  closely  resembled  that  of  honey ;  it 
emulsified  with  ease,  but  almost  immediately  agglutinated  and  refused 
to  be  again  emulsified. 

To  enter  into  a  detailed  description  of  the  characteristics,  morpho- 
logical and  cultural,  of  the  members  of  this  family  is  forbidden  by  the 
scope  of  this  paper^  but  it  will  perhaps  prove  of  service  if  I  tabulate  the 
more  important  points  of  differential  diagnosis  (see  Table  I). 

A  knowledge  of  the  clinical  features  of  the  case  and  of  the  source  of 
the  material  will  assist  one  whose  experience  of  the  morphology  and 
cultural  characteristics  of  these  organisms  is  limited  in  arriving  at  the 
correct  differential  diagnosis. 

The  Micrococcus  catarrhalis  group. — Of  all  the  micro-organisms  in- 
fecting the  respiratory  tract,  this  is  at  once  the  largest,  commonest, 
and  most  widely  distributed  group.  In  the  present  state  of  knowledge 
it  is  a  term  applied  to  all  the  cocci  found  in  these  parts  which  fail  to 
retain  the  stain  by  Gram's  method,  with  the  single  exception  of  the 
meningococcus  or  micrococcus  of  epidemic  cerebro-spinal  meningitis 
(Weichselbaum).  I  have  isolated  at  least  fifty  members  of  this  group 
differing  the  one  from  the  other  in  some  detail,  morphological  or  cul- 
tural;  and  the  following  description  must  be  taken  as  only  applying 
strictly  to  the  form  most  commonly  found  in  catarrhal  infection  of  the 
respiratory  tract.  It  is  a  Gram-negative  coccus,  closely  resembling  the 
gonococcus  in  shape,  and,  like  it,  frequently  growing  in  pairs  ;  it  differs 
from  the  gonococcus  in  being  less  definitely  kidney-shaped,  and  on  the 
whole  larger,  and  in  showing  greater  variation  in  size  ;  every  film  will 
show  some  forms  larger  than  the  majority  and  decolorising  with  less 
ease ;  and  in  the  fact  that  arrangement  into  tetrads  is  quite  common, 
chain-formation  does  not  occur  in  what  is  to  be  regarded  as  the  typical 
Micrococcus  catarrhalis,  aggregation  into  clumps  is  the  rule.  The 
following  table  will  help  in  the  differential  diagnosis  (Table  II). 

Whether  the  smaller  ^s^M^o-catorrAa/is  is  ever  pathogenic  is  doubt- 
ful, and  it  may  be  given  as  a  general  rule  that  the  larger  the  individual 

3 


34 


6 


<: 


5s 

■    1 

05 

+ 
+ 

Throat  and  nose. 

As  a  rule  growth  profuse,  on  plates 
may  attain  diameter  of  Jin. ;  more 
opaque  and  deeper  white  than  any 
of  the  others  ;  centre  raised  and 
ringed. 

Profuse  growth  of  dense  white 
colonies  which  may  coalesce 
(see  Fig.  19). 

Short  ovoid  rods  which  stain  more 
deeply  at  ends;   may  even  fail  to 
stain  in  centre,  so  that  appearance 
may  be  that  of  a  diplococcus  ;   no 
club  forms  (Fig.  23).*     Gram   +. 

Involution  forms  very  few  or  none 

at   all;    rods   longer;    both   ends 

■    roimded,  but  one  end  larger  than 

other ;     unstained    median    band 

more  marked. 

No  polar  granules. 

'0 
re 

_>% 

B.  xerosis. 

o. 

Eye,  nose  rarely. 

Even  after  48  hours  at  37°  scanty 
growth  of  minute  colonies,  round, 
discrete  and  almost  colourless. 

In  24  hours  punctate  colonies 
closely  resembling  those  of  gono- 
coccus  but  drier,  more  granular 
and  more  opaque  (see  Fig.  18). 

Short  rods,  some  of  which  show 
banded  appearance,  some  club 
forms  (Fig.  22).     Gram   +. 

Involution  forms   very    numerous; 
club   forms    -1-  ;     banded   appear- 
ance marked  (Fig.  25). 

S 
re 

re 
"o 

Cu 

0 

C 

re 
< 

c 

■| 

X 
c 

re 

CC 

+ 

Throat. 

Same  as  B.  diphtheria  but  rather 
more  luxuriant. 

As  on  agar  but  more  profuse. 

Short  rods  usually  in  pairs,  each  being 
.shaped  like  aspear  point, the  bases 
being  approximated,  the  points 
directed  away  from  each  other 
(Fig.  21)*  (better  seen  in  methy- 
lene-blue  preparation).    Gram   -1- . 

As  at  24  hours ;  no  invohilion  forms. 

.2 
a. 

0) 

0 

!«! 

OJ 

1) 
_C  - 

tn 
-Ji 

it 
u 

■OD 

u. 

X 

0 

Cu 

6 

< 

-1- 
+ 
-1- 

Throat,  larynx,  nose,  eye. 

Minute  colonies,  rather  larger  than 
those  of  Streptococcus  longus;  dis- 
crete, dull  white,  centre  darker 
than  periphery  by  transmitted 
light,  may  be  almost  brown. 

As  on  agar  but  rather  more  profuse 

■  (see  Fig.  17). 

Very  variable,  wedge  shaped  rods, 
long  cylindrical  rods  (3-4/1  long) 
rods  with  clubbed  swellings  (Fig. 
20).     Gram   +  . 

Involution    forms,    numerous    club 
forms  -1-   (Fig.  24). 

aj 

0) 

Ji 
re 

re 

CU 

C 

C 
CU 

aj- 

cu 
re 

j= 
u 
Oj 
Q- 

T3 

'0 

re 

2  2 

OQ 

."2 
'0 
re       T3 

0       "D 

O 
>^ 

'o 
'c 

re 
CU 

man. 
Sites  where  found 
Growth  on  agar. 

Growth  on  blood- 
agar. 

Microscopic    ap- 
pearance,   with 
Gram's  stain,  lit 
24  hours. 

At  48-72  hours. 

're 

'aj 
2 

Sugar    reactions 

in  3  days  in — 
Glucose  broth. 

Lactose  broth 
Saccharose  broth 
I  Maltose  broth. 

PLATE    VI. 


^  / 


Fig.  22. — B.  xerosis,  twenty-four  hours. 
(Gram.)      x  looo. 


Fig.  22.— B.  septus,  twenty-four  hours. 
(Gram.^      x  lOOO. 


Fig.  24 — Diphtheria  bacillus,  three 
days.     (Gram  )      x  1000. 


''it\ 


>le 


"^ 


Fig.  25.-5.  xerosis,  three  days.    (Gram.) 
X  1000. 


Fig.  26. — B.  septus  and  M.  catarrhalis. 
(Gram  counterstained  neutral  red.) 
X  1000. 


/p%T?>-'   * 


V-i 


'''^'    '^'. 
<'&^^i^^' 


^'^ 


^Jr 


•^ 


PiQ_  27. — M.  catarrhalis.  (Gram 
counterstained  neutral  red.) 
X  1000. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


35 


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36  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

members  of  the  M.  catarvhalis  the  greater  is  the  likelihood  of,  its  being 
pathogenic ;  to  this  statement  there  is,  however,  an  exception ;  there  is 
a  form  which  morphologically  is  a  true  M.  catarvhalis,  except  that  it  is 
in  size  rather  less  than  two  thirds  that  of  a  gonococcus  (see  Fig.  30). 
Culturally,  however,  it  is  favoured  by  anaerobic  conditions,  the  colonies 
on  blood  agar  then  being  much  smaller  than  those  of  the  typical  M. 
catarvhalis,  discrete  and  almost  invisible  instead  of  heaped-up,  aggre- 
gated, crinkled  and  brownish.  It  appears  to  be  strongly  pathogenic, 
and  whether  it  really  belongs  to  the  M.  catarvhalis  group  must  be  left 
an  open  question. 

It  will  be  remembered  doubtless  against  me  that  when  discussing 
the  streptococcus  group  apparent  exception  was  taken  to  value  being 
attached  to  exact  laboratory  research  in  this  domain,  and  I  shall 
certainly  be  exposed  to  a  charge  of  inconsistency  in  advocating  the 
necessity  for  accurate  laboratory  research  being  conducted,  upon  the 
Micrococcus  catarrhalis  group ;  it  is  therefore  incumbent  upon  me  to 
anticipate  this  charge  and  make  a  defence.  What  I  really  objected  to 
in  regard  to  the  streptococcus  group  was  not  the  performance  of 
minute  investigation,  but  the  attachment  of  greater  value  to  pathogenic 
experiments  upon  animals  and  the  reactions  in  various  sugar  media 
than  to  clinical  observation,  a  tendency  which  certainly  has  had  an 
existence,  but  now  happily  is  passing  away. 

The  case  with  the  Micrococcus  catarrhalis  group  is  not  quite  parallel. 
These  micro-organisms  so  far  as  the  respiratory  tract  is  concerned  are 
ubiquitous ;  they  exist,  as  apparently  does  the  streptococcus,  in  every 
mouth  and  throat,  but  they  exist  in  far  greater  variety,  and  under  far 
more  widely  divergent  conditions.  If  in  the  nasal  mucus  of  a  case  of 
acute  rhinitis  a  Micrococcus  catarrhalis  be  found  in  profusion,  little  doubt 
exists  as  to  the  causal  relationship  of  the  bacterium  to  the  disease,  and 
it  is  rare  indeed  to  find  divergent  strains  in  such  a  case;  in  regard  to 
the  sputum,  however,  it  is  quite  another  matter.  From  practically 
every  mouth,  pharynx,  and  naso-pharynx  in  health  or  in  disease 
numerous  Gram-negative  cocci  can  be  recovered,  and  considerable 
variations  will  be  discoverable,  both  morphological  and  cultural.  As  I 
have  said,  I  have  recorded  about  fifty  strains,  differing  in  some  slight 
detail  the  one  from  the  other.  Now  it  will  be  urged  that  there  are  at 
least  two  hundred  strains  of  streptococci;  true,  but  I  believe  that  each  and 
every  one  of  these  is  either  pathogenic  to,  or  capable  of  being  roused 
into  pathogenicity  to,  its  host.  Not  so  with  the  Micrococcus  catarrhalis 
group.  Some,  nay,  most  of  its  members  are  probably  absolutely  devoid 
of  pathogenic  properties,  and  supposing  that  even  half  a  dozen  different 
strains  are  isolated  from  the  materies  inovbi,  we  are  at  present  without 
any  means  whatsoever  of  determining  which  strains  are  responsible  for 


PLATE   VII. 


E,j>^,  i^ 


Fig.   ."!3. — M .  paratetragenus. 
Slightly  reduced. 


Fig.  28. 
(agar). 


-M.  catar.rhalis 
Natural  size. 


F'iG.  29. — M.  catarrhalis 
(blood-agar).  Slightly 
reduced. 


Fig.   34. — Sarcina  lutea. 
Slightly  reduced. 


Fig.  35. — M.  tetragenus. 
Natural  size. 


Fig.  37. — Bacillus  of  Fried- 
lander.     Natural  size. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  37 

the  condition  and  which  are  not,  of  deciding  which  strains  to  incorporate 
in  a  vaccine  and  which  to  leave  out.  We  have  no  alternative  but  to 
include  them  all.  Just  as  I  object  to  over-much  regard  being  paid  to 
the  laborator}'  classification  of  a  streptococcus  and  consequent  neglect 
of  it  as  a  possible  factor  in  the  given  pathological  condition,  so  I  regret 
the  absence  of  a  rehable  method  of  differentiating  the  Micrococcus 
catarrhalis  group,  and  our  consequent  inability  to  separate  strains 
which  are  pathogenic  from  those  which  are  not.  Opsonic  index 
estimations  may  help,  but  are  much  likely  to  prove  of  no  avail ; 
agglutination  tests  are  inadmissible  owing  to  active  spontaneous 
agglutination  in  the  emulsion. 

The  Micrococcus  paratetrageims. — The  first  to  ascribe  pathogenic 
properties  to  this  organism  was  Bezancon.  Benham  has  found  it  in  a 
case  of  pulmonary  abscess,  and  constantly  in  an  epidemic  of  colds.  I 
also  found  it  a  causal  factor  in  almost  every  case  of  catarrh  investigated 
during  two  epidemics.  The  last  two  years  it  has  not  been  in  evidence  ; 
this  year  it  is,  however,  again  occurring  in  a  certain  percentage  of  cases. 
As  its  names  imphes,  it  is  a  micrococcus  usually  occurring  in  tetrads,  but 
also  in  pairs.  These  are  usually  grouped  together  in  a  zooglceal  mass. 
They  are  not  capsulated,  but  both  in  sputum  and  in  culture  films  the 
mucoid  material  faintly  stains,  giving  a  capsular  appearance.  Fig.  31 
is  a  photo-micrograph  of  a  smear  of  sputum  showing  dark  masses  of 
Micrococcus  paratetragenus  and  more  faintly  stained  bacillus  of  Fried- 
lander.  Fig.  32  shows  admirably  the  appearance  of  a  stained  film 
of  a  pure  culture.  The  more  darkly  stained  kidney-shaped  tetrads 
are  seen  imbedded  in  the  faintly  stained  zooglceal  mass.  The 
Micrococcus  paratetragenus  is  the  best  of  all  instances  of  organisms  which 
may  be  styled  Gram  ±.  Unless  decolorisation  with  absolute  alcohol  be 
very  complete  the  gentian  violet  will  be  retained,  feebly  but  definitely, 
so  that  even  two  minutes'  staining  with  neutral  red  will  fail  to  displace  it. 
Strictly  I  think  it  should  be  regarded  as  a  Gram-positive  organism.  In 
smears  it  is  apt  to  be  confused  with  the  Micrococcus  tetragenus  and  with 
the  Sarcina  liitea ;  from  the  former  it  is  differentiated  by  its  larger  size 
and  peculiar  staining  properties  (compare  Figs.  32  and  36),  from  the  last 
by  its  smaller  size,  from  both  by  its  cultural  properties  {cf.  Figs.  33,  34 
and  35). 

It  grows  well  on  agar  (Fig.  33  ;  cf.  Fig.  34  of  Sarcina  lutea  and  Fig.  35 
oi  Micrococcus  tetragenus),  better  on  blood-agar.  When  sown  thinly  the 
colonies  are  white,  rounded,  dry,  umbonate  ;  they  adhere  to  the  medium 
like  the  Micrococcus  catarrhalis,  and  emulsify  with  some  difficulty ;  once 
emulsified,  however,  there  is  little  or  no  tendency  to  spontaneous 
agglutination.  Heating  to  6o°-yo°  C.  aids  emulsification,  whereas  with 
Micrococcus  catarrhalis  it  often  tends  to  stronger  agglutination;  when 


38  THK    BACTERIAL    DISEASES    OE    RESTIRATKJN. 

sown  thickly  it  forms  heaped-up  masses.     In  both  it  produces  some 
turbidity  and  a  slimy  deposit  on  the  bottom. 

I  have  found  it  form  a  small  amount  of  acid  from  the  following 
sugar  media  :  dextrose,  levulose,  saccharose,  galactose,  lactose,  and 
from  mannitol. 

The  Micrococcus  tetragenus  has,  I  think,  often  been  confused  with  the 
Micrococcus  paratetragenus,  which  in  several  ways  it  closely  resembles. 
It  also  is  a  kidney-shaped  coccus,  arranged  in  pairs  or  fours,  and 
surrounded  by  a  gelatinous  pseudo-capsule,  which  stains  faintly  (well 
seen  in  Fig.  36).  It  is,  however,  distinctly  smaller,  about  two  thirds 
the  size,  and  is  definitely  Gram-positive.  It  is,  unlike  the  M.  paratetra- 
genus, a  pyogenic  organism,  producing  in  laboratory  animals  an  abscess 
locally  and  a  rapidly  progressing  septicaemia  generally. 

On  agar  it  forms,  relatively  to  the  paratetragenus,  small  colonies 
(Fig.  35),  which  are  white,  slightly  elevated,  shiny,  and  moist;  the 
borders  are  at  first  even,  later  sinuous  in  outline.  When  growing  on 
plates  it  gives  forth  an  odour  like  glue.  In  broth  it  leaves  the  medium 
clear  and  forms  a  moderate  precipitate,  which  on  shaking  rises  as 
flocculi  and  then  disperses. 

It  forms  acid  in  glucose  and  lactose. 

The  bacillus  of  Friedlander  group  includes  a  considerable  number  of 
organisms  presenting  slight  variation.  In  the  secretions  they  occur 
usually  in  pairs,  each  individual  surrounded  by  a  wide  capsule  (see  Fig.  i, 
March  number). 

The  rods  vary  considerably  in  length  (o"5-3"5  ju)  and  have  rounded 
ends.  They  are  non-motile,  stain  readily  with  any  dye,  but  lose  the  stain 
by  Gram's  method  and  take  on  the  neutral  red  (Fig.  38).  They  grow 
with  extreme  luxuriance  upon  or  in  almost  every  medium. 

On  gelatine  and  agar  plates  when  sown  thinly  the  colonies  may 
attain  a  diameter  of  even  a  quarter  of  an  inch.  They  are  round,  grey  to 
white,  iridescent,  elevated,  and  slimy,  so  that  on  slopes  they  readily 
coalesce  and  may  run  down  to  the  bottom  of  the  tube  (Fig.  37)  ;  the 
water  of  condensation  becomes  turbid.  Deep  colonies  in  plates  are 
oval  or  whetstone  shaped.  Gelatine  is  not  liquefied.  In  a  gelatine  or 
agar  stab  well-developed  growth  occurs,  giving  the  appearance  of  a 
string  of  pearls,  while  on  the  surface  an  elevated  growth  like  a  nail-head 
is  formed.  On  potato  a  thick,  moist,  shiny  growth  yellow  or  greyish- 
brown  in  colour  rapidly  develops.  Growth  in  broth  is  also  luxuriant,  the 
medium  becoming  quite  cloudy  and  a  slimy  deposit  forming.  Almost 
all  the  sugar  media  are  rapidly  fermented  with  formation  of  both  acid 
and  gas. 

In  working  upon  the  bacteriology  of  the  respiratory  tract  frequently 
one  meets  with  organisms  possessing  characteristics  varying  more  or 


PLATE   VIII. 


Fig.  30. — M.  catarrhalis,  small  t_\'pe. 
(Gram  counterstained  neutral  red.) 
X  1000. 


Fig.  31. — Bacillus  of  Friedlander  and  If. 
paratt'trai(enu^  in  sputum.  (Gram 
counterstained  neutral  red.)       x  looo. 


l'"lG.   32. — yi .  pnratetrngeiuis.      (Gram 
counterstained  neutral  red.)      x  1  000. 


«? 


'■^A^iK^i^:.:- 


Fig.  36. — y/ .  tetrageniLS. 
(Gram.)      x  1000. 


Fig.  38  — Bacillus  of  Friedlander. 
(Gram  counterstaiaed  neutral 
red.)      X  1000. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  39 

less  from  the  above.  They  may  be  capsulated  or  not  capsulated,  they 
may  be  motile  or  non-motile,  definitely  Gram  — ,  or  tending  to  retain  the 
stain,  they  may  or  may  not  liquefy  gelatine,  on  agar  form  a  dry  or  slimy 
white  or  almost  colourless  growth,  in  a  stab  culture  form  the  typical  moist, 
heaped  up,  nail-head  growth,  or  a  dry,  porcelain-like  diffuse  growth, 
ferment  all,  some  or  none,  of  the  sugars. 

In  any  one  or  more  of  these  particulars  variations  may  be  seen  ;  thus 
there  are  all  gradations  between  the  typical  bacillus  of  Friedlander  as 
described  above  and  the  Bacillus  proteus. 

The  Bacillus  proteus  vulgaris,  as  its  name  implies,  is  a  very  pleomorphic 
organism  ;  it  may  occur  as  slender  rods  varying  in  length  from  i  to  4  /x 
in  length,  as  long  straight  or  spiral  threads.  It  is  actively  motile,  and 
does  not  form  capsules. 

Its  staining  by  Gram's  method  is  variable.  Lehmann  and  Neu- 
mann have  no  doubt  that  it  is  Gram-positive ;  other  observers  are  equally 
certain  that  it  is  Gram-negative;  personally  I  regard  it  as  Gram- 
negative. 

Like  the  bacillus  of  Friedlander  almost  any  medium  is  suited  to  its 
growth.  On  gelatine  it  forms  a  delicate,  grey,  transparent  growth,  but 
rapidly  liquefies  the  medium.  On  agar  it  forms  grey,  slimy,  transparent, 
rounded  colonies.  In  broth  it  forms  considerable  turbidity  and  abun- 
dant precipitate.  Milk  is  coagulated  and  then  liquefied.  On  potato 
it  forms  a  scanty  yellowish  growth  with  a  dull  lustre.  In  the  various 
sugar  media  it  forms  abundant  gas  and  acid. 

Alone  it  would  appear  only  infrequently  to  give  rise  to  pathological 
conditions  of  the  respiratory  tract  and  its  adnexa  ;  more  often  it  is  asso- 
ciated with  other  pathogenic  organisms.  I  have  isolated  it  in  pure 
culture  from  several  chronic  cases  of  bronchial  and  Eustachian  catarrh 
and  middle-ear  disease  ;  as  these  cases  have  recovered  rapidly  upon 
exhibition  of  the  autogenous  vaccine  its  causal  relationship  to  the 
conditions  was  more  or  less  confirmed. 

The  Bacillus  pyocyanewi  (the  bacillus  of  green  or  blue  pus)  is  an 
actively  motile  Gram-positive  bacillus,  usually  in  the  form  of  slender  rods 
(1*5-6  ju)  long,  but  sometimes  very  short  and  plump,  sometimes  almost 
threadlike.  It  is  characterised  by  the  yellow-green  or  blue-green 
fluorescence  which  it  produces  in  the  media  upon  or  in  which  it  grows, 
and  by  the  early  liquefaction,  at  first  cup-shaped,  later  cylindrical, 
which  it  produces  in  a  gelatine  stab.  That  alone  it  is  capable  of  pro- 
ducing pathological  conditions  is  certain ;  at  the  same  time  when 
present  in  such  affections  of  the  respiratory  tract  and  its  adnexa  as 
ulcers  of  the  mouth  and  pharynx,  otitis  media  and  pulmonary  abscesses^ 
it  usually  occurs  associated  with  other  pathogenic  organisms,  and  the 
difficulty  of  determining  its  precise  role  is  not  lessened  by  the  following 


40  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

considerations  :  (i)  that  in  a  given  condition  which  is  remaining  more 
or  less  stationary  the  B.  pyocyaneiis  may  be  present  for  a  few  days,  dis- 
appear for  a  time,  then  reappear — perhaps  again  to  disappear  of  its  own 
accord ;  (2)  that  two  other  bacteria  which  appear  to  be  entirely  non- 
pathogenic very  closely  resemble  the  B.  pyocyaneus,  viz.  the  B.  fliLorescens 
liquefaciens  and  B.  fluorescens  non-liqiiefaciens.  The  former  is  indistin- 
guishable from  the  B.  pyocyaneus  in  its  morphology  and  cultural  reactions, 
except  that  it  does  not  coagulate  milk,  and  is  said  to  be  non-patho- 
genic to  animals.  The  latter  is  differentiated  by  its  failure  to  liquefy 
gelatine. 

Unless,  therefore,  the  B.  pyocyaneus  appears  to  be  the  sole  invader  or 
is  present  in  overwhelming  numbers  in  a  characteristic  pus,  I  feel 
disposed  as  a  rule  to  give  it  a  chance  of  spontaneously  disappearing; 
when,  however,  it  fails  to  do  this,  or  the  patient  does  not  make  adequate 
progress  under  treatment  with  the  vaccines  of  its  co-invaders,  I  feel  the 
time  has  come  to  use  its  vaccine.  At  the  same  time  it  must  be  granted 
that  if  money  is  no  object  to  the  patient  the  immediate  exhibition  of 
the /'_yoc)'a7?^«s  vaccine  in  suitable  doses,  either  alone  or  in  combina- 
tion with  other  vaccines  which  may  be  indicated,  is  hardly  likely  to 
have  any  ill-effects  and  may  be  productive  of  good. 

The  B.  coli  commnnis  is  so  well  known  and  so  adequately  described 
in  all  text-books  of  bacteriology  that  little  need  be  said  about  it  beyond 
pointing  out :  (i)  That  it  is  said  fairly  frequently  to  complicate  pul- 
monary tuberculosis;  personally  I  have  found  it  rarely.  (2)  That  it  is 
often  present  in  lung  abscesses  and  in  empyemata,  especially  if  these  be 
of  long  standing ;  as  a  rule  it  is,  however,  not  the  primary  infection, 
and  unless  the  discharge  itself  be  carefully  examined  and  plating-out 
be  conducted  with  unusual  care  the  pneumococcus,  streptococcus  or 
B.  influenzcs,  which  constituted  the  primary  infection,  may  easily  be 
missed,  and  the  consequent  treatment  with  a  coli  vaccine  lead  to  not 
entirely  satisfactory  results.  (3)  That  occasionally,  after  abdominal 
operations,  it  may  produce  a  diaphragmatic  pleuris}'  or  basal  pneu- 
monia, progressing  later  to  an  empyema.  I  have  seen  such  ensue  after 
fixation  of  a  kidney,  the  whole  abdominal  cavity  remaining  free  from 
active  infection.  (4)  That  in  the  secretions  the  B.  coli  often  retains 
the  Gram  stain  so  strongly  that  unless  the  treatment  with  absolute 
alcohol  be  thoroughly  performed  the  bacilli  may  appear  to  be  Gram- 
positive  ;  the  cultural  tests  will,  however,  resolve  all  doubt. 

The  B.  typhosus  I  merely  mention  for  this  reason  :  It  is,  I  believe, 
a  far  more  frequent  factor  in  the  production  of  typhoid  pneumonia  than 
is  commonly  realised.  In  the  sputum  of  such  cases  careful  search 
should  be  made,  not  only  for  the  typhoid  bacillus,  but  also  for  the 
pneumococcus  and  streptococcus,  for  in  cultures  the  first  will  overgrow 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  4I 

the  latter  two.  \'accine  treatment,  in  my  opinion,  offers  much  the 
best  hope  of  recover\-  in  these  cases,  but  success  is  largely  determined 
by  accuracy  in  the  diagnosis  of  the  responsible  bacteria. 

The  organisms  associated  with  follicular  tonsillitis  and  pyorrhcea 
alveolaris  are  legion  in  number.  Some  recent  experiments  of  my  own 
have  shown  what  intensely  toxic  products  are  formed  by  some  of  these, 
while  Mncent's  fusiform  bacillus  has  recently  been  shown  to  be  pos- 
sessed of  definitely  pyogenic  properties.  Cases  ha\-e  been  recorded  of 
acute  dermatitis  and  abscess  formation  as  resulting  from  bites,  and 
from  these  the  fusiform  bacillus  has  been  recovered  in  pure  culture  ;  it 
would  also  appear  to  be  the  cause  of  a  peculiar  form  of  sore  very 
prevalent  in  some  of  the  South  Sea  Islands.  Strictly  anaerobic  con- 
ditions greatly  favour  its  artificial  culture. 

Most  of  these  mouth  organisms  stain  but  faintly  with  most  of  the 
dves,  and  for  the  stud\-  of  their  morphology  weak  carbol  fuchsin  is  to 
be  recommended. 


CHAPTER     IV. 

B(iii).  RESULTS  OF  OBSERVATIONS  INTO  THE  BACTE- 
RIOLOGY OF  THE  VARIOUS  DISEASED  CONDITIONS 
OF   THE    RESPIRATORY   TRACT. 

Any  attempt  at  determining  the  precise  role  played  by  a  given 
bacterium  in  the  causation  of  pathological  conditions  of  the  respiratory 
tract  is  beset  by  numerous  difficulties.  The  enumeration  of  a  few  only 
of  these  will  help  to  show  how  real  these  difficulties  are. 

(i)  As  one  who  has  been  working  continuously  on  the  subject  for 
nearly  ten  3^ears  I  am  obliged  to  confess  that  one's  views  as  to  what 
may  be  and  are  not  causal  factors  have  been  steadily  changing;  an 
organism  which  one  now  knows  beyond  doubt  to  be  concerned  in  a  given 
process  was  not  even  considered  seven  years  ago,  and  carefully  as  all 
records  have  been  kept,  an  uneasy  suspicion  is  aroused  that  observa- 
tions even  five  years  old  are  not  as  trustworthy  as  one  would  like  them 
to  be. 

(2)  The  results  of  examinations  of  smears  of  secretion  are  not  always 
confirmed  by  the  results  of  plating  experiments;  for  instance  a  smear 
may  show  vast  numbers  of  what  appear  to  be  B.  influenzce,  while  a 
plate  prepared  from  the  same  secretion  may  after  even  three  days'  in- 
cubation fail  to  show  a  single  colony  of  that  bacterium  ;  confirmation 
therefore  is  lacking  of  the  identity  of  the  bacillus  seen  in  the  smear. 

(3)  Again,  the  predominant  organism  seen  in  smears  may  not  be  the 
predominant  organism  found  in  cultures,  and  even  if  it  be  granted 
that  the  former  observation  is  more  likely  to  give  a  true  picture  of  the 
bacteriology  of  the  condition  than  is  the  latter,  we  are  faced  by  doubts 
as  to  whether  the  predominant  organism  necessarily  is  responsible  for 
the  condition  rather  than  one  of  those  which  is  present  in  relatively  few 
numbers.  As  the  result  of  experience  I  would  say  that  in  settling  this 
question  much  depends  upon  the  stage  of  the  disease.  To  take  one  ot 
the  simplest  examples,  at  the  very  beginning  of  an  attack  of  acute  nasal 
catarrh  the  Staphylococcus  albtis  may  alone  be  detected  in  the  excreted 


THE    BACTERIAL    ])ISEASES    OF    RESPIRATION.  43 

mucus  and  in  cultures  of  swabs  from  the  middle  turbinals;  three  or  four 
days  later  the  Bacillus  septus  may  reign  supreme  to  the  total  exclusion 
of  all  other  organisms ;  after  yet  another  interval  of  three  or  four  days 
Staphylococcus  albus,  B.  septus  and  M.  catarrhalis  may  all  be  present, 
and  the  first  or  last  of  these  three  may  predominate.  Even  more 
complex  may  be  the  results  of  observations  upon  the  secretions  in  a 
case  of  acute  or  subacute  sinusitis  or  bronchial  catarrh. 

(4)  Observations,  if  they  are  to  have  a  definite  value,  must  be 
extended  over  a  considerable  space  of  time.  As  I  shall  show  presentl}', 
the  results  of  observations  made,  say,  last  year  are  very  dissimilar  to 
those  of  observations  made  five  years  previously;  this  would  appear  to 
be  due  to  the  fact  that  either  the  pathogenicity  of  the  various  organisms 
to  man  rises  and  wanes,  or  the  resisting  powers  of  the  human  race 
tovv'ards  a  given  bacterium  are  exalted  and  depressed  in  turn.  Due 
allowance  must  therefore  be  made  for  this  in  the  compilation  of  statistics 
as  to  the  relative  frequencies  with  which  the  various  bacteria  indicated 
are  concerned  in  the  several  pathological  conditions.  For  instance, 
during  the  four  years  1905-1908  I  found  the  B.  influences  in  only  2*4  per 
cent,  of  the  cases  of  respiratory  catarrh  which  I  examined,  whereas 
during  the  three  years  igog-igii  it  was  present  in  over  40  per  cent,  of 
the  cases  investigated.  It  thus  follows  that  to  the  percentage  figures 
obtained  from  my  own  long-continued  observations,  either  alone  or 
combined  with  the  results  of  other  investigators  over  shorter  periods, 
undue  importance  must  not  be  attached;  they  have  a  certain  value  and 
a  certain  interest,  but  that  is  all. 

(5)  That  whereas  the  truly  acute  attack  is  capable  of  differentia- 
tion from  the  truly  chronic  it  is  by  no  means  easy  to  know  under  which 
category  to  place  the  subacute,  and  still  less  easy  to  know  how  to 
deal  with  the  findings  in  an  acute  attack  upon  a  chronic  one.  Of  all 
the  catarrhal  organisms  there  is  only  one  which,  with  very  rare  excep- 
tions, gives  rise  to  acute  attacks  alone  and  not  to  chronic,  viz.  the 
B.  septus. 

(6)  That  it  is  very  rare  for  the  most  strictl}'  localised  infection  to 
remain  localised  for  long ;  the  simplest  nasal  catarrh  in  the  greater 
majority  of  cases  is  soon  complicated  by  an  infection  of  one  or  other  of 
the  sinuses  ;  inasmuch  as  this  sinusitis  usually  clears  up  rapidly  of  its 
own  accord  its  presence  easily  escapes  recognition.  Again,  in  the 
latter  stages  of  nasal  and  post-nasal  catarrh,  when  the  secretion  has 
become  thick  and  difficult  to  expel,  forcible  efforts  at  its  expulsion 
result  in  a  temporary  dilatation  of  the  Eustachian  tube  or  tubes  and 
consequently  their  frequent  infection.  This,  again,  as  a  rule,  speedily 
subsides.  Occasionally,  however,  infection  persists  in  both  instances, 
the  sinuses  or  tubes  becoming  infected  by  the  bacteria  resident  in  the 


44 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


parts  at  the  time  of  infection,  whereas  the  bacteriology  of  the  nasal  or 
post-nasal  catarrh  is  liable  subsequently  to  undergo  a  change,  secondary 
invaders  in  whole  or  part  taking  the  place  of  the  primary  ones.  It  is 
therefore  not  necessarily  to  be  expected  that  the  bacteriology  of  the 
nasal  mucous  membrane,  of  the  antrum  and  the  frontal  sinus  will  be  the 
same  in  a  case  of  extension  of  the  infection  of  a  chronic  nasal  catarrh. 
Or  again,  an  acute  rhinitis  due  to  the  pneumococcus  may  extend 
steadily  down  the  respiratory  tract  until  finally  a  pneumococcal 
bronchitis  is  set  up,  or,  as  perhaps  is  more  usual  with  this  organism^ 
a  pneumococcal  laryngitis  may  extend  simultaneously  upwards  and 
downwards,  so  that  at  the  end  of  about  five  days  a  condition  of  acute 
rhinitis  and  bronchitis  has  superseded  the  primary  laryngitis.  The 
difficulty,  therefore,  of  classifying  the  conditions  accurately  is  by  no 
means  a  small  one.  With  these  reservations  I  proceed  to  give  a  few 
statistics  of  the  bacteriological  findings  by  various  observers  in 
catarrhal  conditions  of  the  respiratory  tract. 


(i)  In  Nasal  and  Post-nasal  Catarrh. 

Table  III. 

Bacteriology  of  Nasal  and  Post-nasal  Catarrh  (R.  W.  Allen's  figures, 
1905  to  1911  inclusive). 


1905-08. 

1909.  • 

1910. 

1911. 

1909-11. 

Number  of  cases 

42 

34 

35 

34 

Per 

Per 

Per 

Per 

Average 

cent. 

cent. 

cent. 

cent. 

per  cent 

B.  influenza 

.      1=2-4 

16  =  47 

II    =  31 

17 

=  50 

43 

Pneumococcus 

.      0=0 

23  =  68 

25  =  71 

18 

=  53 

66 

Streptococcus 

.     0=     o(?) 

4  =  12 

II   =  31 

23 

=  68 

41 

M.  catanhalis 

•  19  =  45 

17  =  50 

29  =  83 

22 

=  65 

66 

M.  paratetragenus  . 

.     0  =    0  (?) 

5  =  14 

9  =  27 

4 

=   12 

18 

B.  septus 

■   18  =  43 

9  =  24 

11=31 

7 

=  20 

26 

Bacillus  of  Friedlander  . 

•  13  =  31 

2=5 

I  =    3 

2 

=    6 

5 

Allowing  for  the  fact  that  the  absence  of  streptococci  during  the 
period  of  1905-08  was  probably  more  apparent  than  real,  inasmuch  as 
I  did  not  then  recognise  it  as  a  factor  in  the  production  of  post-nasal 
catarrh,  the  most  striking  features  are  the  great  contrast  in  the 
frequency  with  which  the  B.  infltienzce  and  pneumococcus  was  found 
in  the  two  periods  1905-08  and  1909-11.  In  the  Lancet  of  February 
13th,  1909,  p.  500,  I  recorded  the  incidence  of  this  pneumococcal 
epidemic  which  has  persisted  till  the  present  time ;  the  influenzal 
epidemic  began  about  two  months  later,  and  whereas  the  pneumo- 
coccus is  now  showing  a  tendency  to  die  out,  the  B.  inflnenzcB  has  a& 
yet  shown  no  such  tendency.  The  type  of  concurrent  complications- 
has,    moreover,    changed,    neuritis    and    herpes    zoster   having   been. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


45 


prevalent  of  late  to  the   more    or    less  exclusion   of  pneumonia  and 
gastric  disturbances. 

The  B.  septus  on  the  other  hand  appears  to  have  lost  much  of  its 
virulence ;  during  the  past  twelve  months  its  incidence  has  declined  by 
nearly  one  half,  and  such  cases  as  are  due  to  it  have  been  very  mild 
and  short. 

Table  IV. 
Dy.  C.  H.  Benhajii's  Figures  for  Cases  of  Common  Cold. 

Number  of  cases 

B.  infliienzce 

Pneumococcus 

Streptococcus  . 

M.  catarrhalis   . 

M.  paraietragenus 

B.  septus    . 

Bacillus  of  Friedlander 

(possibly  more) 

Dr.  Benham  and  myself  have  compared  our  results  from  time  to 
time,  and  such  discrepancies  as  exist  in  our  percentage  figures  for 
1905-og  were  largely  due  to  the  fact  that  the  pneumococcus-influenzal 
epidemic  at  the  very  end  of  1908  and  beginning  of  igog  appeared  to 
reach  London  before  Brighton,  whereas  the  reverse  was  the  case  in 
the  instance  of  the  M.  paratetragenus,  which  also  failed  to  gain  the 
same  foothold  in  London  that  it  did  in  Brighton;  these  peculiarities 
we  noted  at  the  time. 


Nov.  1905-Jan.  1906. 

1907-08. 

1908-09. 

1905-09. 
Total. 

27 

14. 

49 

.     go 

Per 

Per 

Per 

Average 

cent. 

cent. 

cent. 

per  cent. 

■     3  =  II     • 

4  =  28 

6  =   15 

.       16 

.  (?)  =  (?)     . 

2  =  14 

2=     5 

•       5 

.     6  =  22     . 

4  =  28 

II   =  27 

.     26 

.  13  =  48     . 

13  =  93 

21   =  52 

.     58 

.     3  =  II     • 

14  =  100 

25  =  62 

•     52 

.  24  =  88     . 

II   =:  78 

.       25  =  62 

•     74 

der     .     1=4  (?) 

3  =  21 

5  =   12 

.     II 

Table  V. 

Dr.  Will  Walter's  Figures  for  igo8-og  in  100  Cases  of  Rhinitis  {Journ. 
Amer.  Med.  Assoc.,  September  24th,  igio,  p.  iogi-iog6). 


B.  influenza 

Pneumococcus 

Streptococcus 

M.  catarrhalis 

M.  paratetragenus 

B.  septus 

B.  Friedlander 


2   =   2  per  cent. 

•  7  =  7 
•5=5 
.  20  =  20 
(?)  12  =  12 
•  •  35  =  35 
■7   =   7 

Swabs  were  taken  from  the  nasal  mucosa  alone  and  cultures  made 
on  Loeffler's  blood-serum,  a  medium  which  Walter  subsequently  recog- 


46  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

nised  as  not  altogether  suitable  for  the  purpose ;  .  the  results,  therefore, 
are  not  strictly  comparable  with  those  of  Benham  and  myself. 

Table    VI. 

C.  E.  Wesfs  Figures  for  50  Cases  of  Chronic  Post-nasal  Catarrh  (Proc. 
Roy.  Soc.  Med.,  February,  1911,  Otological  Section,  p.  43). 


B.  infliienzcr         .         .         . 

0=0 

per 

cent. 

Pneumococcus    . 

•     35  =  70 

,1 ) 

Streptococcus     .         . 

.     12  =  24 

)) 

M.  catarrhalis 

(?)  10  —   20 

,, 

M.  paratetragenns 

(?) 

B,  septus 

1=2 

5 ) 

B.  Ffiedlander 

6  =  12 

j> 

Staphylococcus  aureus    . 

.    13  =  26 

>) 

The  period  of  time  over  which  these  investigations  were  made  is  not 
mentioned.  Swabs  were  taken  from  the  pharyngeal  vault  by  means  of  a 
guarded  swab ;  direct  observations  from  smears  of  the  swabs  do  not 
appear  to  have  been  made,  and  cases  of  acute  nasal  catarrh  were  care- 
fully excluded,  so  that  these  findings  are  not  to  be  compared  with  those 
of  the  previous  observers.     The  chief  points  to  be  noticed  are  : 

(i)  The  high  percentage  figure  for  the  pneumococcus,  \\z.  70  per 
cent.,  which  very  closely  corresponds  to  my  own,  viz.  66  per  cent,  for 
all  cases  of  nasal  and  post-nasal  catarrh,  acute  and  chronic,  during  the 
three  years  igog-i I. 

(2)  The  very  low  figure  for  the  Bacillus  septus,  which  also  coincides 
with  my  own  observation  of  recent  months.  I  am  therefore  inclined 
to  view  West's  figures  merely  as  representing  the  bacteriological  con- 
ditions in  post-nasal  catarrh  during  a  limited  period  of  time  and  as 
corresponding  to  the  incidence  of  pneumococcal  infection  of  the  res- 
piratory tract  generally. 

(3)  The  complete  absence  of  the -B.  influenzcs  I  can  only  attribute 
to  the  omission  of  observations  upon  direct  smears  and  to  a  possible 
insufficient  incubation  period  for  the  culture  plates.  During  the  past 
twelve  months  the  B.  influenzce  has  been  very  slow  of  development. 

(4)  The  high  percentage  incidence  of  the  Staphylococcus  auretts.  West 
considers  it  a  frequent  factor  in  the  production  of  chronic  post-nasal 
catarrh  and  I  am  inclined  to  agree  that  it  sorrtetimes  is. 

To  summarise,  it  would  appear  that  any  of  the  seven  organisms,  B. 
injluenzce,  pneumococcus,  streptococcus,  M.  catarrhalis,  M.  paratetra- 
genns, B.  septus,  and  bacillus  of  Friedlander,  alone  or  in  varying  corn- 
binations,  may  be  responsible  for  a  catarrhal  condition  of  the  upper 
respiratory  passages.     In  perhaps  40  per  cent,  of  cases  one  organism  so 


THE    BACTERIAL    DISEASES    OE    RESPIRATION.  47 

predominates  as  to  justify  the  conclusion  that  it  is  the  cause  of  the 
attack  ;  more  often  two  or  more  organisms  are  associated  toget^ier,  the  B. 
influenzcB  with  the  pneumococcus  or  M.  paratetragemis,  the  B.  septus 
with  the  M.  catarrhalis  or  M.  paratetragenus,  so  that  it  becomes  verv 
difficult  to  decide  which  organism  or  organisms  stand  in  a  directly 
causal  relationship  to  the  attack.  My  own  belief  is  that  mixed  infections 
from  the  beginning  are  fairly  common. 

In  uncomplicated  purulent  nasal  catarrh  the  streptococcus  is  the 
most  frequent  cause,  next  to  it  the  Staphylococctis  aureus.  When  sinus 
complications  co-exist  the  B.  influenzce  and  pneumococcus  are  by  far 
the  most  frequent  bacteria  concerned. 

(2)  In  Diseases  of  the  Accessory  Sinuses. 

The  observations  of  Torne  {Central  f.  Bakt.  «.  Parasii.,  Jena,  1903, 
vol.  iii,  pp.  250-255)  upon  36  cadavera  in  which  the  sinuses  were  found 
to  be  healthy  would  seem  to  indicate  that  in  health  these  parts  are 
remarkably  free  from  bacteria ;  thus  in  22  instances  which  were 
examined  within  two  and  a  half  hours  of  death  the  sterility  was 
complete ;  of  the  remaining  14,  which  were  examined  between  three 
and  tvvent3'-four  hours  after  death,  7  were  sterile,  7  contained  a  few 
bacteria.  He  also  examined  26  cavities  in  26  cadavera ;  3  of  these 
which  were  acutely  inflamed  were  examined  within  one  and  a  quarter 
hours  of  death,  and  in  all  the  pneumococcus  was  present,  in  i  case 
along  with  the  Staphylococcus  aureus.  In  12  cases  which  showed  a 
chronic  purulent  condition  the  bacteriology  was  most  varied,  strepto- 
coccus. Staphylococcus  aureus,  pseudo-catarrhalis,  spirilla,  proteus,  B.  coli, 
and  Friedlander's  bacillus  being  among  those  found.  Of  the  11  cavities 
which  showed  slight  catarrhal  changes  upon  examination  within  three 
hours  of  death,  9  were  sterile,  i  contained  Staphylococcus  aureus,  i 
Bacterium  sputigeninn . 

Herzfeld  and  Hermann  {Arch,  fur  Laryngol.  u.  Rhinol.,  Berlin,. 
1895)  described  the  bacteriology  of  10  cases  of  antral  suppuration 
examined  during  life ;  streptococci  were  present  in  8,  staphylococci 
in  7,  in  both  cases  always  along  with  other  organisms,  B.  protects 
in  2,  B.  coli  in  3  ;  one  only  was  monorganismal,  and  that  was  due  to 
the  bacillus  of  Friedlander.  Whether  these  observers  made  direct 
examinations  from  smear  as  well  as  from  culture  films  I  do  not  know, 
and  it  is  also  to  be  noted  that  at  this  time  the  B.  influenzce  was  not  as 
yet  a  well-known  organism  and  may  have  been  missed. 

The  results  of  Lewis  and  Logan  Turner  {loc.  cit.)  are  very  interesting.. 
They  examined  57  cases  of  antral  disease,  no  other  sinuses  being 
involved,  i  of  ethmoidal  sinusitis,  4  of  frontal  sinusitis,  and  12  antral 
cases  complicated  by  involvement  of  the  ethmoidal  and  frontal  cells. 


48 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 
The  results  in  the  57  uncomplicated  antral  cases  were  as  follows : 

Table  VII. 


Streptococcus 
Pneumococcus 
Staphylococcus  albus  . 
Ps.-Diphtheria  B. 
B.  proteus 
B.  inesenterictis 
B.  Hojfmanni  . 
Staphylococcus  aureus 
B.  suhtilis 
B.  septus  . 


43  cases  =  75"4  per  cent. 


42 
40 
8 
6 
6 
5 
5 
3 


=  74-1 
=  70T 

=  14 
=  10-5 
=  10-5 
=  87 
=  87 
=  5*2 
=    3*5 


They  also  took  swabs  from  27  cavities  during  operation 
from  the  nose  after  posturing  in  42  instances. 
The  comparative  results  are  as  follows : 


and  swabs 


Pneumococcus 
Staphylococcus 
Streptococcus 
Ps.-Diphtheria  B. 
Hoffmann's  B. 

B.  pyocyaneus,  B. 


Table  VIII. 

Direct  from  cavity, 
cases. 

21  =  777  per  cent. 

21  =  777 
21  =  777 


Nasal  swab. 


29  =  70     per  cent. 
28  =  66-6 
27  =  64-3 
8  =  19 
5  =  II 
xerosis,  B.  perfriugens,  leptothrix,  spirillum,  and 
B .  plexiformis  were  each  found  in  one  instance  in  swabs  taken  direct 
from   the  antrum,    while  B.  influenzcB,   B.    Friedlander,   B.   coli,    and 
B.  huccalis  maximus  were  each  found  only  in   swabs  from  the  nose; 
these  usually  showed  a  more  profuse  flora  than  did  those  taken  direct 
at  operation. 

In  cases  of  less  than  one  year's  duration  staphylococcus  and  pneumo- 
coccus were  present  in  84-6  per  cent.,  and  streptococcus  in  6r6  per 
cent.,  whereas  in  more  chronic  cases  streptococcus  was  present  in 
So  per  cent.,  pneumococcus  in  70  per  cent.,  and  staphylococcus  in 
66  per  cent.  The  almost  total  absence  of  the  B.  influenzcz  (one  case 
only)  is  to  be  accounted  for  by  the  probable  absence  of  any  influenza 
epidemic  during  the  time  of  their  observations  or  within  a  year  or 
two  prior  to  them. 

The  one  ethmoidal  case  was  a  chronic  one  and  showed  Streptococcus 
pyogenes  and  Staphylococcus  aureus. 

In  the  3  cases  of  frontal  sinusitis  the  findings  were  pneumococcus 
and  Staphylococcus  cereusflavus  in  one,  staphylococcus,  streptococcus  and 


THE    BACTERIAL    DLSEASES    OF    RESPIRATION. 


49 


B.  coli  in  the  second,  pneumococcus,  Staphylococcus  albns  and  auyeus  Sind 
Sirepiococcus  brevis  in  the  third. 

From  an  experience  of  30  cases  of  sinusitis  examined  during  the 
years  1909-10-11  I  am  unable  to  agree  with  Lewis  and  Logan  Turner's 
figures,  my  results  having  been  as  follows  : 


Table 

IX. 

1909. 

1910. 

[91 

. 

Total 

10 

9 

II 

30 
Mean 

Per 

Per 

Per 

Per 

cent. 

cent. 

cent. 

cent. 

•     7  =  70     . 

6=  67 

9 

= 

82 

=  73 

•     5  =  50     . 

6=  67 

3 

= 

27 

=  47 

2  =  20 

3  =  33 

5 

= 

45 

=  33 

•     4  =  40     . 

7  =  78 

4 

= 

36 

=  50 

— 

I  =  II 

I 

= 

9 

=  7 

— ' 

— 

I 

= 

9 

=  3 

— 

— 

I 

= 

9 

=  7 

•     3  =  30     . 

I  =  II 

0 

= 

18 

=  20 

— 

— 

I 

=r 

9 

=  3 

Number  of  cases 


Bacillus  influenzcB    . 

Pneumococcus 

Streptococcus 

M.  catarrhalis . 

M.  paratetragenus     . 

B.  septus 

Bacillus  of  Friedlander 

Staphylococcus 

B.  coli    . 


In  most  instances  examinations  were  conducted  upon  secretion 
obtained  from  the  nose  after  posturing ;  in  a  few  instances,  however,  in 
which  the  material  was  also  obtained  either  at  operation  or  through 
an  old  operation  aperture,  the  results  differed  little  in  the  two  cases  ; 
the  nasal  secretion  tending,  as  Lewis  and  Logan  Turner  pointed  out,  to 
present  a  slightly  more  complex  liora.    All  the  cases  were  chronic  ones. 

One  of  the  cases  was  a  very  interesting  one  of  ethmoidal  sinusitis 
and  greatly  distended  ethmoidal  bulla ;  it  was  seen  in  conjunction  with 
Mr.  Herbert  Tilley.  The  predominant  organism  was  the  B.  influenzcB; 
streptococci  were  also  present,  and  a  very  few  -V.  catarrhalis. 

If  comparison  of  these  results  be  made  with  the  findings  set 
out  in  Table  III  for  nasal  and  post-nasal  catarrh  during  the  same  period 
a  general  correspondence  will  be  seen  ;  this  would  probably  be  more 
marked  if  cases  of  post-nasal  infection  were  excluded  from  Table  III.  It 
is,  however,  to  be  noted  that  nasal  infections  by  the  B.  influenza:  seem 
especially  prone  to  extend  their  energies  in  the  direction  of  the  acces- 
sory sinuses.  The  high  incidence  of  the  Micrococcus  catarrhalis  is  almost 
certainly  to  be  attributed  to  nasal  swabs  having  been  employed  in  the 
majority  of  my  cases  ;  their  numbers  relative  to  the  B.  influenza:,  pneu- 
mococcus or  streptococcus  in  any  given  case  were,  as  a  rule,  quite  low. 

What  I  have  already  emphasised  in  connection  with  the  statistics 
for  nasal  catarrh  I  again  emphasise  here  :  Percentage  figures  have  little 

4 


50  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

value  unless  correlated  over  a  long  term  of  years ;  they  are  entirely 
dependent  upon  what  organism  or  organisms  exhibit  special  virulence 
during  the  period  of  observation.  Again,  there  is  no  a  priori  reason 
why  the  infecting  agent  should  not  change  from  time  to  time.  The  B. 
inflitenzcB,  for  instance,  may  lose  its  virulence  and  even  the  power  of 
maintaining  a  saprophytic  existence,  and  be  replaced  by  a  pneumo- 
coccus  which  is  then  exhibiting  particularly  pathogenic  properties,  this 
latter,  in  its  turn,  being  supplanted  by  a  more  hardy  streptococcus ; 
such  a  series  of  changes,  in  one  or  two  instances,  I  have  had  an  oppor- 
tunity of  observing. 

Finally,  in  multiple  sinusitis  it  must  be  remembered  that  the 
bacteriology  of  one  infected  cavity  may  differ  totally  from  that  of  another 
even  adjacent  one.  Since  then  the  secretion  obtained  on  one  occasion 
may  come  from,  say,  a  frontal  cell,  and  that  obtained  on  another  occasion 
from  an  antrum  or  ethmoidal  cell,  this  must  not  be  taken  as  neces- 
sarily meaning  a  change  of  infecting  agent  in  the  event  of  dissimilar 
findings ;  this  is  a  pitfall  which  one  must  carefully  avoid. 

(3)  In  Eustachian  Catarrh  and  Otitis  Media. 

The  recognition  of  Eustachian  catarrh  as  a  frequent  cause  of 
preventable  deafness  is  becoming  increasingly  clear ;  its  genesis  is 
usually  in  a  precedent  nasal  or  post-nasal  catarrh.  Forcible  efforts 
at  expulsion  of  the  nasal  mucus  during  the  stage  of  thickened 
secretion  result  in  dilatation  of  the  Eustachian  tubes,  and  occa- 
sionally in  the  driving  of  some  infected  material  into  their  orifices. 
This  danger  is  greatly  increased  by  the  use  of  nasal  douches — a 
practice  highly  commendable  in  itself,  but  one  necessitating  con- 
siderable care.  Every  patient  when  ordered  to  use  a  nasal  douche 
should  be  warned  of  this,  and  told  to  allow  the  douche  fluid  to  run 
away,  and  not  to  use  any  forcible  efforts  at  expulsion  of  it  with 
its  contained  bacteria  and  dissolved  mucus  until  the  cavities  have 
been  thoroughly  washed  out.  Another  hint  I  have  found  to  have 
decided  value :  by  firmly  pressing  the  tragus  of  the  ear  with  a  finger- 
tip into  the  external  meatus,  counter-pressure  is  extended  through  the 
tympanum  into  the  middle  ear  and  Eustachian  tube,  and  the  risk  of 
dilatation  considerably  reduced.  I  have  noted  that  with  most  people 
one  tube  as  a  rule  dilates  much  more  readily  than  the  other,  and  that 
if  counter-pressure  be  applied  to  the  side  more  liable  to  dilatation  the 
douche  fluid  and  mucus  may  then  be  forcibly  expelled  without  danger 
to  the  Eustachian  tube. 

This,  then,  being  the  wa}'  in  which  Eustachian  catarrh  is  perhaps 
commonly  set  up,  it  follows  that  the  bacteriology  of  Eustachian  catarrh 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  5  I 

should  correspond  to  that  of  nasal  and,  more  especiall}^,  post-nasal 
catarrh.  Unfortunately,  reliable  observations  are  lacking  owing  to  the 
almost  insuperable  difficulties  of  obtaining  swabs  free  from  contamina- 
tion with  nasal  or  pharyngeal  mucus.  The  few  observations  upon 
which  any  reliance  could  be  placed  that  I  have  been  enabled  to  make, 
by  the  kindness  of  Dr.  Greville  Macdonald,  Mr.  G.  S.  Hett,  and  others, 
have  tended  to  show  that  the  M.  catarrhalis,  B.  influenzcE,  pneumo- 
coccus,  and  streptococcus  are  the  bacteria  which  most  commonly  set 
up  catarrh  of  the  Eustachian  tube  ;  upon  one  occasion  B.  septus  was 
obtained  in  pure  culture  from  a  swab  taken  from  the  orifice.  Clinical 
observation  would  tend  to  confirm  these  results,  as  the  colds  due  to 
these  four  organisms  are  more  particularl}-  the  ones  in  which  signs  of 
involvement  of  the  Eustachian  tubes  are  most  evidenced. 

That  many,  if  not  most,  cases  of  otitis  media  are  sequent  to 
Eustachian  catarrh  is  probable.  In  scarlet  fever  and  measles  the 
streptococci  almost  certainly  find  their  way  to  the  middle  ear  via  the 
Eustachian  tube.  This,  however,  is  not  the  only  route;  typhoidal 
otitis  media,  for  instance,  probably  arises -from  the  blood  infection,  and 
the  same  may  be  true  of  some  pneumococcal  and  influenzal  cases. 
The  B.  coli  group,  B.  proteus  group,  and  staphylococci  also  give  rise  to 
this  condition,  while  otitis  media  due  to  the  B.  pyocyaneus,  spirochaetes 
and  streptothrix  has  been  reported ;  as  these  organisms  are  fairly 
common  inhabitants  of  the  mouth,  infection  via  the  tube  is  probable  in 
these  cases. 

(4)  In  Tracheitis  and  Laryngitis. 

Here,  again,  reliable  bacteriological  observations  are  lacking,  but  the 
probable  truth  can  be  deduced  from  clinical  observations  in  the  follow- 
ing way.  There  are  certain  definite  clinical  types  of  catarrhs  which  at 
one  time  or  another  in  their  course  involve  the  larynx  and  trachea. 
The  bacteriological  findings  remaining  more  or  less  constant  throughout 
the  attack,  the  inference  appears  to  be  justified  that  the  bacteria  which 
are  responsible  for  the  nasal,  post-nasal,  bronchial  and  pulmonary 
catarrh  are  likewise  responsible  for  the  tracheitis  and  laryngitis.  For 
instance,  we  have  the  three  following  types  of  catarrh  :  (i)  Definitely 
located  in  the  larynx  there  is  a  dry,  rough  feeling  as  if  sand-paper  had 
been  employed  to  line  the  space,  the  rough  surface  towards  the  mucous 
membrane.  This  gives  rise  to  a  dry,  hard  cough,  which  in  a  day  or  two 
may  become  paroxysmal ;  after  a  severe  fit  of  coughing  a  tiny  pellet  of 
mucus,  clear  and  very  viscid,  may  be  expelled.  The  infection  extends 
upwards  and  downwards  simultaneously,  so  that  at  the  end  of  three  to 
five  days  the  bronchi  are  definitely  involved,  mucous  rales  and  rhonchi 
are  to  be  heard  in  the  chest,  while  nasal  and  post-nasal  discharge  is 


52  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

abundant.  The  mucus  is  no  longer  clear  and  viscid,  but  yellow,  muco- 
purulent, tending  to  be  nummular,  and  easily  spread  upon  a  slide. 
This  is  a  description  of  a  type  of  cold  during  the  course  of  which  prac- 
tically nothing  but  pneumococcus  is  to  be  seen  in  the  secretions, 
whether  this  be  the  tiny  pellet  expelled  from  the  larynx  during  the  first 
day  or  two  or  in  the  later  muco-purulent  discharge.  The  pneumo- 
coccus may  therefore  be  assumed  to  have  been  responsible  for  the 
initial  laryngitis.  (2)  A  second  type  begins  in  a  very  similar  manner 
and  may  likewise  extend  down  into  the  chest  and  up  into  the  nose ; 
the  secretion,  however,  remains  clear  and  viscid  throughout,  and  in  it 
the  M.  paratetragenus,  sometimes  in  pure  culture,  sometimes  along 
with  the  M.  catarrhalis  or  pneumococcus,  is  to  be  found.  The 
M.  paratetragenus  would  therefore  appear  to  cause  a  laryngitis.  (3) 
Again,  a  dry,  harsh  feeling  of  the  soft  palate  and  post-nasal  space  may 
be  followed  in  twenty-four  to  thirty-six  hours  by  an  acute  rhinitis ;  the 
infection  then  spreads  steadily  down  the  larynx  and  trachea  into  the 
large  bronchi.  Cough  is  marked,  but  rarely  paroxysmal,  and  copious, 
thin,  clear  mucus,  only  in  the  later  stages  streaked  here  and  there  with 
muco-purulent  strands,  is  easily  voided.  This  type  of  cold  appears  to 
be  due  to  the  M.  catarrhalis,  but  as  other  bacteria  are  commonly 
present  in  the  secretions  from  the  beginning  it  is  with  less  certainty 
that  one  can  attribute  the  laryngitis  and  tracheitis  to  the  M.  catarrhalis 
alone ;  however,  such  I  believe  to  be  the  case. 

Similarly,  the  B.  influenzcB,  and  with  less  certainty  the  streptococcus, 
appear  to  be  capable  of  setting  up  this  condition.  On  the  other  hand, 
I  have  never  found  these  parts  involved  in  catarrhal  conditions  due  to 
the  B.  septus  or  bacillus  of  Friedlander.  As  regards  the  latter,  how- 
ever, inasmuch  as  at  times  it  does  attack  the  chest,  it  is  highly  pro- 
bable that  it  is  capable  of  acclimatising  itself  in  the  trachea  and 
larynx.  I  can  only  say  that  with  an  experience  of  eighteen  catarrhal 
attacks  due  to  the  Bacillus  of  Friedlander  I  have  never  seen  these  parts 
involved. 

Roughly,  in  order  of  importance,  I  should  arrange  the  causes  of 
acute  catarrhal  laryngitis  and  tracheitis  as  follows :  Pneumococcus, 
B.  influenzce,  M.  catarrhalis,  M.  paratetragenus.  It  is  hardly  necessary 
for  me  to  emphasise  the  fact  that  I  am  here  dealing  only  with  purely 
catarrhal  conditions  ;  the  diphtheria  bacillus  is,  of  course,  the  most 
important  invader  by  far  of  the  larynx  and  trachea,  next  to  it  the 
tubercle  bacillus. 

(5)  In  Pulmonary  Catarrh,  Bronchitis,  and  Asthma. 

The  deeper  down  the  respiratory  tract  the  source  from  which  the 
secretion  is  voided,  the  greater  obviously  the  danger  of  contaminating 


THE    BACTERIAL    DISEASES    OE    RESPIRATION. 


53 


bacteria  being  picked  up  on  the  wa}- ;  the  uncleanHness,  from  the 
bacteriological  standpoint,  of  the  fauces  and  mouth  I  have  already 
alluded  to,  and  it  would,  at  first  sight,  appear  to  be  almost  impossible 
to  conduct  reliable  observations  upon  material  coming  from  the  bronchi, 
bronchioles,  or  pulmonary  cells.  Such,  however,  is  not  the  case.  The 
precautions  outlined  on  pp.  9  and  10  will  reduce  the  adventitious  microbes 
to  a  minimum,  and  a  knowledge  of  the  cytology  of  the  sputum,  as  out- 
lined on  pp.  13-15,  will  enable  us  to  decide  whether  the  actual 
sample  under  examination  has  been  voided  from  the  desired  locality. 
In  Table  X  are  set  out  the  results  of  my  examinations  in  pulmonary 
catarrh  and  bronchitis  during  the  three  years  1909-11. 


Table 

X. 

1909. 

1910. 

1911. 

Total. 

Number  of  cases 

51 

33 

20 

.        104 

Per 

Per 

Per 

Mean 

cent. 

cent. 

cent. 

percentage 

B.  inflnenzcB 

21    =  42      . 

9  =  27     . 

12    =   60 

.         40 

Pneumococcus  . 

22   =   44      . 

18  =  54     • 

14   =   70 

•          52 

Streptococcus    . 

21    =   42       . 

20  =  60     . 

14   =   70 

•       53 

M.  catarrhalis     . 

36   =  72       . 

23  =  69     . 

16  =   80 

.       72 

M.  paratetragenus 

12    =    24       . 

9  =  27     . 

3  =  15 

•       23 

Bacillus  of  Friedlander 

group    . 

5  =  10     . 

1=3- 

I  =    5 

7 

B.  septus     . 

1=2. 

— 

I  =     5 

2 

Streptothrix 



— 

3  =  15 

3 

If  comparison  of  these  results  be  made  with  those  for  the  same  years 
for  nasal  catarrh  set  out  in  Table  III,  the  only  point  of  material  difference 
will  be  seen  to  be  in  what  I  have  already  referred  to — the  great  dis- 
inclination of  the  B.  septus  to  make  its  habitat  in  the  lower  respiratory 
passages.  These  figures  must  also  be  taken  as  representative  only  of  the 
infecting  agents  during  the  years  1909-11  ;  should  any  given  organism 
lose  its  virulence,  naturally  it  will  cease  more  or  less  to  appear  as  an 
infective  agent  in  the  lower  respiratory  tract,  just  as  it  will  do  in  regard 
to  the  upper  passages. 

One  other  point  is  deserving  of  attention,  namely  this,  that  infections 
of  the  lower  tract  are  commonly  mixed  ones,  more  commonly  so, 
perhaps,  than  are  those  of  the  upper  ;  the  reason  of  this  I  take  to  be  the 
fact  that  infections  of  the  lower  passages  frequently  follow  on  those  of  the 
upper,  and  that  these  latter,  as  the  attack  progresses,  tend  to.  become 
more  and  more  mixed  infections.  The  Micrococcus  catarrhalis  alone,  for 
instance,  certainly  is  able  to  initiate  and  maintain  an  acute  bronchial 
infection,  but  more  commonly  it  appears  as  a  secondary  infection  to  the 


54 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


pneumococcus  or  B.  influenza.  Pure  influenzal  infections,  again,  are 
relatively  uncommon  ;  more  often  they  are  complicated  by  the  pneumo- 
coccus or  streptococcus. 

The  importance  of  the  pneumococcus  as  the  causative  agent  for 
certain  cases  of  acute  suffocative  catarrh  has  been  well  brought  out  by 
Samuel  West  {Proc.  Roy.  Soc.  Med.,  April,  igii,  Med.  Sect.,  p.  loi),  and 
I  am  inclined  to  regard  this  organism  as  at  the  same  time  the  most  fre- 
quent cause  of  bronchial  catarrh  and  the  most  dangerous  to  the  patient. 
It  is  also  worthy  of  notice  that  the  B.  influenzcB  may  be  resident  in  the 
bronchi  or  pulmonary  cells,  giving  rise  to  marked  constitutional,  but 
few  localised,  symptoms ;  indeed  the  sputum  voided  may  be  almost  nil. 

The  findings  in  asthma. — As  will  be  quite  apparent  when  I  come  to 
consider  the  vaccine  therapy  of  asthmatic  conditions  I  am  very  far 
from  considering  bacteria  as  the  universal  cause  of  asthma,  but  regard 
them  merely  as  one  of  the  excitants  of  the  asthmatic  attack,  as  one  of 
the  agents  capable  of  stimulating  the  nerve-endings  and  unstable 
centre.  Where  bronchitic  symptoms  are  prominent  the  importance  of 
bacteria  is  correspondingly  greater.  During  the  years  igog-ii 
I  investigated  the  flora  of  the  sputum  collected  with  suitable  pre- 
cautions a  few  hours  after  the  commencement  of  the  attack  in  fifty-one 
cases.     The  results  are  set  out  in  Table  XI. 


Table  XI. 

1909. 

1910. 

1911. 

Total. 

Number  of  cases    . 

29 

Per 

cent. 

II  . 

Per 
cent. 

II   . 

Per 
cent. 

51 

Mean 
percentage 

B.  influenzcB  .  ■ 

3  =  10 

.       2=      18 

.     I  =      g     . 

==  12 

Pneumococcus 

7  =  23 

•4-36 

.     2  =    18 

=  26 

Streptococcus 

26  =  go 

.    II  =  100 

.  II  =  100     . 

=  g6 

M.  catarrhalis 

18  =  62 

•     8=    73 

.  10  =    gi     . 

=  72 

M .  paratetragenus  . 

4  =  13 

•     3=    27 

•     3=    27     . 

=  20 

Comparison  of  these  results  with  those  set  out  in  Tables  III  and  X 
brings  out  several  points  of  interest.  The  low  percentage  incidence  of 
the  B.  influenzcB  and  pneumococcus  is  very  marked,  but  when  they  do 
occur  their  significance  I  believe  to  be  correspondingly  greater.  The 
almost  universal  occurrence  of  the  streptococcus  group  is  most  striking, 
and  corresponds,  I  believe,  to  its  aetiological  importance.  The  two 
chief  varieties  of  streptococcus  found  have  been  already  described  on 
pp.  28-30.  The  incidence  of  the  M.  catarrhalis  and  M.  paratetra- 
genus is  approximately  the  same  in  all  three  tables,  and  their  impor- 
tance in  asthma  is  very  difficult  to  determine.    The  organism  described 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  5  5 

by  Carmalt-Jones  as  a  possible  cause  of  asthma  he  now  tells  me  he  is 
inclined  to  regard  as  belonging  to  the  M.  catarrhalis  group. 

One  thing  which  will  certainly  strike  the  investigator  into  the 
bacteriology  of  respiratory  affections  is  the  much  less  complexity  of  the 
findings  in  the  asthmatic  sputum  as  compared  with  that  derived  from 
other  catarrhal  affections.  The  total  number  of  bacteria  present  is  not 
only,  as  a  rule,  much  less,  but  monorganismal  and  binorganismal 
specimens  are  much  more  frequently  encountered. 

(6)  In  Whooping-Cough. 

Lack  of  material  has  prevented  me  making  any  extended  investiga- 
tions of  my  own  upon  this  question.  The  very  careful  and  laborious 
investigations  of  Freeman  at  St.  Mary's  Hospital  and  of  Martha  Wol- 
lenstein  in  America  have  fortunately  rendered  any  further  work  almost 
quite  unnecessary.  These  observers  corroborate  the  work  of  others, 
and  regard  the  establishment  of  the  bacillus  of  Bordet-Gengou  as  the 
specific  cause  of  whooping-cough  as  quite  complete.  They  have,  how- 
ever, in  addition  brought  out  this  important  point  :  infection  is  very 
rarely  a  pure  one;  simultaneous  or  secondary  infection  by  the  B.influenzcB 
exists  in  a  very  large  percentage  of  cases  (nearly  go  per  cent.),  while 
the  same  holds  true  of  the  pneumococcus  to  a  considerably  smaller  yet 
important  degree.  This  accounts  for  the  modified  success  which  has 
attended  the  treatment  of  whooping-cough  by  means  of  a  vaccine  of 
Bordet's  bacillus  alone,  and  will  be  more  fully  referred  to  subse- 
quently. 

(7)  In  Pulmonary  Phthisis. 

In  this,  the  most  important  of  all  infections  of  the  respiratory  tract, 
accuracy  in  the  diagnosis  of  the  organisms,  which  accompany  the  tubercle 
bacillus,  becomes  more  than  ever  necessary.  Fortunately  the  secretion 
from  a  lung  affected  by  phthisis  by  its  very  nature  is  much  less  likely 
to  pick  up  contamination  as  it  is  voided  than  is  the  sputum  of  other 
infections.  Provided  the  precautions  detailed  for  the  collection  of  speci- 
mens on  pages  9  and  10  are  carefully  followed,  the  nummular  masses 
of  sputum  only  require  washing  twice  or  thrice  in  sterile  salt  solution 
to  free  them  from  adventitious  microbes;  or  instead  of  washing,  a 
suitable  sample  may  be  placed  in  a  well-heated  platinum  dish  for  a  few 
seconds ;  it  is  then  turned  over  and  the  other  side  likewise  cooked ; 
by  means  of  a  sterile  knife  the  mass  may  then  be  incised  and  specimens 
taken  for  direct  and  cultural  examinations  from  the  cold  interior.  Of 
course,  when  the  sputum  is  not  nummular  the  preliminary  precautions 
must  be  carried  out   with    especial   care.      Personally,    I    direct    my 


56 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


patients  to  make  but  one  expectoration  into  a  bottle,  and  prefer  the 
early  morning  specimen ;  at  the  same  time  it  is  well  to  take  two  or 
three  other  specimens  at  intervals  during-  the  day,  each  in  a  separate 
bottle,  for  it  by  no  means  follows  that  the  secondary  infection  at  one 
focus  of  tuberculous  disease  will  correspond  to  that  at  a  second  or 
third.  How  the  importance  of  such  organisms  as  are  isolated  in  the 
diseased  processes  can  be  determined  by  laboratory  and  by  clinical 
tests  I  shall  detail  later.  Observations  upon  the  bacteria  concerned  in 
conditions  other  than  that  of  pulmonary  phthisis  consumed  so  much  of 
the  eight  years'  period  which  I  have  devoted  to  the  study  of  the 
bacterial  diseases  of  the  respiratory  tract  that  it  is  only  during  the  last 
three  years  that  I  have  been  able  to  study  the  mixed  infections  of 
phthisis  with  adequate  care.  The  results  of  my  observations  are  set 
out  in  Table  XII. 

Table  XII. 

The  Mixed  Infections  of  Pulmonary  Phthisis. 


1909. 

1910. 

1911. 

Total. 

Number  of  cases     . 

.     14    . 

12  . 

16 

42 

Per 

Per 

Per 

Mean 

cent. 

cent. 

cent. 

percentage 

B.  infiuenzcB 

I  =     7 

— 

6 

=    38 

=  15 

Pneumococcus     . 

3  =  21 

5  =42 

7 

=  43     • 

=  33 

Streptococcus 

II  =78 

9  =75 

14 

=  87     . 

=  81 

M.  catarrhalis 

12  =  86 

10  =  83 

10 

=  62 

=  76 

M.  paratetragenus 

5  =  30 

4  =  33 

I 

=     6 

=  22 

B.  septus 

I  =    7 

— 

— 

=    2 

Bacillus  of  Friedlander 

I  =    7 

— 

I 

=     6     . 

=    4 

S.  albtis 

1=    7 

4  =  33 

.     2 

=  12 

=  16 

S.  aureus 

— 

.2  =  16 

3 

=  19 

=  12 

Proteus 

I  =    7 

— 

I 

=z  6 

■     =    4 

B.  coli 

— 

— 

— 

— 

The  yearly  variations  from  the  mean  are  b}'  no  means  inconsider- 
able in  the  instance  of  some  of  the  bacteria,  the  B.  influenzce,  pneumo- 
coccus, and  M .  paratetragenus,  for  example ;  this,  as  before,  may  be  due 
to  a  periodic  rise  and  fall  in  the  pathogenicity  of  these  micro-organisms. 
One  point  which  I  feel  is  worthy  of  attention  is  this  :  there  is  a  great 
tendency  to  speak  of  these  as  secondary  infections ;  the  term  mixed 
infection  is  far  preferable,  for  such  evidence  as  we  have  supports  the 
view  that  in  many  instances  the  pneumococcus,  B.  influenzce  or  strepto- 
coccus is  the  primary  infection,  that  by  the  tubercle  bacillus  the  secon- 
dary one. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  57 

The  small  percentage  of  cases  in  which  I  have  found  the  staphy- 
lococcus to  be  concerned  is  somewhat  striking,  the  percentages  of  cases 
also  in  which  I  have  found  the  B.  influenza  and  pneumococcus  present 
are  also  considerably  lower  than  in  the  cases  of  pulmonary  catarrh  and 
bronchitis  for  the  same  years  (vide  Table  X),  but  correspond  much 
more  closely  with  the  figures  for  asthma  {vide  Table  XI),  as  does  also 
the  percentage  figure  for  the  streptococcus. 


CHAPTER   V. 

THE    VACCINE    THERAPY    OF    RESPIRATORY    DIS- 
ORDERS. 

IV  (a)  General  considerations. — As  vaccine  treatment  is  essentially 
nothing  more  nor  less  than  an  attempt  at  the  artificial  stimulation  of 
such  means  of  defence  against  bacterial  invasion  as  the  tissues  of  the 
body  already  possess  when  these  threaten  to  make  default,  it  is 
obviously  necessary  first  to  consider  what  are  the  defensive  mecha- 
nisms of  the  body  against  the  bacterial  invasion  of  the  parts  now 
under  conside^ration. 

As  we  have  already  seen,  nature  has  endowed  man  with  a  bacterial 
filtration  apparatus  at  the  very  vestibule  of  the  true  respiratory  tract. 

The  nasal  vibrissse  and  ciliated  epithelial  cells  with  their  coating 
of  sticky  mucus  act  as  a  filter  of  quite  extraordinary  efficiency.  Some 
years  ago  I  endeavoured  to  estimate  the  actual  number  of  bacteria 
which  escaped  involvement  in  the  nasal  passages  in  the  case  of  purely 
nasal  respiration  of  London  air.  Accurate  observations  proved  very 
difficult  to  perform,  and  I  obtained  too  few  thoroughly  satisfac- 
tory ones  to  make  them  worthy  of  publication.  The  conclusion, 
however,  appeared  to  be  justified  that  at  least  95  per  cent,  of  the 
organisms  entering  the  nose  were  entrapped  therein,  and  accordingly 
failed  to  appear  in  the  respiratory  air  as  it  entered  the  larynx ;  of  the 
remaining  5  per  cent,  or  less  by  far  the  greater  percentage  must  be 
caught  up  by  the  ciliated  epithelium  of  the  larynx  and  trachea  ;  still,  as 
we  have  seen,  a  certain  number  do  undoubtedly  enter  the  bronchi  and 
reach  the  lung. 

What,  then,  is  the  fate  of  these  entangled  bacteria  ?  The  state- 
ment has  been  made  that  the  respiratory  mucus  possesses  bactericidal 
properties.  This  I  have  proved  beyond  question  to  be  wrong  ;  that  it 
may  be  inhibitory  of  bacterial  growth  to  a  slight  extent  is  possible, 
but  this  my  own  experiments  fail  entirely  to  confirm. 

It  would  thus  appear  that  the  function  of  the  mucus  is  a  purely 


THE    BACTERIAL    DISEASES    OF    RESPIRATKjX.  59 

mechanical  one  ;  in  health  when  it  is  secreted  in  small  amount  it 
serves  merely  to  entangle  the  bacteria  and  prevent  their  access  to  the 
pulmonary  tissues  ;  in  pathological  conditions  it  is  increased  in  amount, 
and  serves  in  addition  to  wash  the  multiplying  bacteria  and  their 
toxic  products  away  from  the  inflamed  areas.  Such  bacteria  as 
succeed  in  penetrating  this  defence  have  now  to  meet  the  opposition  of 
the  epithelial  cells.  No  cells  of  the  body  would  appear  to  be  possessed 
of  more  strongly  phagocytic  powers  than  these  epithelial  cells  of  the 
upper  respiratory  tract ;  both  in  the  healthy  and  pathological  state  they 
are  always  to  be  seen  crowded  with  bacteria.  How  far  their  phagocytic 
power  is  independent  of  the  co-operation  of  opsonins  and  other 
immune  bodies  has  not  been  determined,  but  that  their  inherent 
phagocytic  power  is  very  considerable  is  beyond  question. 

As  a  rule  these  defensive  agencies  suffice  to  protect  the  upper 
respiratory  passages  against  bacterial  attacks ;  at  times,  however,  the 
virulence  or  number  of  the  micro-organisms  may  be  such  that  the 
outworks  are  penetrated  and  the  inner  lines  of  defence  attacked.  The 
lymphoid  cells  and  polynuclear  leucocytes  now  have  their  parts  to 
play,  and  herein  probably  receive  considerable  assistance  from  the 
immune  bodies  of  the  tissues.  Should  these  prove  incapable  of 
localising  the  conflict  systemic  infection  may  result,  as  is  sometimes 
seen  in  the  case  of  the  B.  influenzce,  B.  tuberculosis  and  pneumococcus, 
and  the  lymph-nodes,  liver,  spleen,  and  pulmonary  tissues  are  involved 
in  the  struggle,  filtering  off  and  destroying  the  invaders  with  the 
assistance  of  the  opsonins,  lysins,  agglutinins,  and  other  immune 
bodies.  Granting  the  truth  of  these  views  it  becomes  at  once  apparent 
that  inasmuch  as  "immune  bodies"'  play  but  a  subordinate  role  in 
protecting  the  respiratory  passages  against  bacterial  invasion,  if  we 
rest  content  merely  with  the  endeavour  to  stimulate  the  over-produc- 
tion of  ''immune  bodies"'  by  the  artificial  introduction  into  healthy 
tissues  of  the  corresponding  bacterial  vaccines,  we  shall  be  failing  in 
our  full  duty  to  the  patient.  Let  us  then  consider  what  are  the 
essential  preliminaries  to  any  scheme  of  vaccine  treatment. 

First  and  foremost,  it  is  little  use  that  nature  has  endowed  man  with 
an  efficient  bacterial  filter  if  from  various  causes  he  fail  to  avail  himself 
of  it.  Nasal  respiration  is  a  habit  which  should  be  taught  in  the 
cradle,  and  far  too  seldom  is.  No  nurse  or  mother  should  allow  an 
infant  to  sleep  with  the  mouth  open ;  gentry  closing  it  when  the  child 
is  asleep  will  usually  suffice  ;  should  this  not  be  the  case,  then  an 
elastic  band  may  be  fixed  gently  over  the  point  of  the  chin  in  order  to 
secure  the  desired  result ;  this  will  have  the  additional  good  effect  of 
preventing  the  child  sucking  its  thumb,  and  so  distorting  the  palatal 
arch.  The  due  observance  of  these  precautions  will  do  much  to  obviate 


6o  thp:  bacterial  diseases  of  respiration. 

the   subsequent  appearance    of    enlarged   tonsils    and    uvula,   and    of 
adenoid  growths. 

When  these  occur  in  children  who  do  not  perform  nasal  respiration 
careful  training  in  the  habit  will  frequently  suffice  to  cause  their  dis- 
appearance ;  should  this,  however,  not  result,  or  should  nasal  respiration 
prove  impossible  from  their  presence,  surgical  measures  must  perforce 
be  taken,  and  careful  training  be  then  begun. 

In  the  event  of  the  patient  having  already  reached  adolescence  or 
mature  life  attention  to  this  point  becomes  even  yet  more  urgent. 
Deflections  of  the  septum,  enlarged  turbinate  bones,  polypi,  adenoids 
or  enlarged  tonsils  may  each  render  nasal  respiration  difficult,  or  even 
impossible,  to  carry  out.  In  this  case  surgical  measures  should  be 
insisted  on,  and  their  performance  encouraged  by  assuring  the  patient 
that  they  alone  will  frequently  suffice  to  rid  him  of  all  his  troubles 
without  recourse  being  had  to  a  long  and  costly  course  of  therapeutic 
immunisation. 

When  abnormalities  have  been  adequately  dealt  with  it  still  remains 
to  teach  the  habit  of  nasal  respiration.  This  procedure  can  be  made  not 
altogether  unattractive  to  the  patient  in  the  following  way.  Note  is 
made  of  the  maximum  power  of  expanding  the  chest,  and  he  is  given 
these  instructions  :  A  watch  is  to  be  placed  by  the  bedside  in  such  a 
position  that  it  can  readily  be  seen  when  the  patient  is  lying  in  bed  flat 
upon  the  back.  A  very  low  pillow,  or  none  at  all,  is  placed  under  the 
head,  and  the  dorsal  position  assumed,  legs  straight  and  arms  by  the 
side,  the  only  covering  a  single  sheet.  The  lungs  are  now  emptied  as 
completel}'  as  possible,  the  residual  air  being  got  rid  of  by  means  of 
two  or  three  forcible  little  expirations,  and  by  bringing  each  arm 
firmly  over  the  points  of  the  opposite  shoulder.  The  arms  are  now 
replaced  by  the  side,  and  air  taken  in  through  the  nose  as  slowly  as 
possible ;  when  the  lungs  are  apparently  full  it  will  be  found  that  a 
little  more  air  can  still  be  taken  in  by  slightly  arching  the  back  and 
drawing  back  the  shoulders.  The  time  is  now  noted,  and  the  breath 
held  ;  after  a  certain  interval  the  patient  will  feel  that  he  can  hold  it 
no  longer  ;  as  he  becomes  more  and  more  practised  he  will  find  that 
in  reality  he  can  retain  the  air  until  long  after  the  head  begins  to  swim, 
but  this  may  well  be  left  until  some  proficiency  has  been  attained.  A 
glance  is  then  given  at  the  time,  and  forcible  expiration  performed  as 
speedily  as  possible  through  the  open  mouth. 

The  whole  procedure  is  then  begun  ab  initio  and  repeated  only 
twice.  This  is  done  regularly  night  and  morning.  It  is  no  uncommon 
experience  of  mine  to  find  that  a  patient  who  at  the  beginning  of  a 
course  could  retain  the  breath  for  no  more  than  forty-five  seconds,  will 
at  the  end  of  four  to  six  weeks'  practice  retain  it  with  even  greater  ease 


thp:  bacterial  diseas?:s  of  respiration.  6i 

for  quite  two  minutes,  and  that  the  chest  expansion  has  meanwhile 
gone  up  from  f- 1  in.  to  2-2y  in.  Some  patients  regard  this  training 
as  an  attractive  competition  with  themselves.  It  then  remains  to  urge 
that  whenever  they  are  in  the  country  walking  on  the  hills  or  heath, 
that  they  should  remember  several  times  to  fill  and  empty  their  lungs 
completely. 

In  certain  cases  slight  modifications  have  to  be  made ;  for  instance, 
asthmatic  cases  should  be  advised  that  thorough  expiration  is  even 
more  important  than  thorough  inspiration  ;  emphysematous  cases  must 
be  warned  to  conduct  the  exercises  with  due  discretion,  that,  inasmuch 
as  damage  has  already  resulted  to  the  pulmonary  tissues,  which  are 
unduly  thin  and  fragile,  too  forcible  inspiratory  and  expiratory  move- 
ments are  to  be  avoided  lest  further  damage  be  the  result. 

Not  only  will  this  training  in  correct  respiratory  methods  render 
nasal  respiration  easier  of  performance  until  finally  it  becomes  a  habit, 
but  improved  nutrition  of  the  tissues  generally,  and  thereby  increased 
power  of  elaborating  immune  bodies  therein  and  so  of  resisting  bacterial 
attacks,  will  be  brought  about. 

On  p.  9  I  have  referred  to  the  supreme  importance  of  scruti- 
nising the  mouth  thoroughly  for  the  presence  of  pyorrhoea  alveolaris 
and  follicular  tonsillitis.  It  is  little  use  endeavouring  to  free  a  nasal 
cavity  of  streptococcus  or  Micrococcus  catarrhalis  by  the  injection  of 
the  corresponding  vaccine  w'hen  there  are  pockets  round  the  teeth 
or  in  the  tonsils  filled  with  these  bacteria,  more  or  less  inaccessible 
both  to  the  action  of  immune  bodies  and  phagocytic  cells.  Crowns 
and  bridges  in  a  mouth  I  look  upon  as  an  utter  abomination,  and 
have  never  yet  seen  the  mouth  containing  them  in  anything  but 
a  highly  septic  state.  The  practice,  too,  of  leaving  in  the  mouth 
one  or  two  teeth  around  whose  margins  pyorrhoea  exists  merely  for 
the  better  fixation  of  a  denture  is  again  a  proceeding  which  cannot  be 
too  strongly  condemned.  Even  if  the  micro-organisms  responsible  for 
the  pyorrhoea  are  in  no  way  concerned  in  the  respiratory  condition, 
yet  the  toxins  they  elaborate  are  so  potent  that  a  general  lowering  of 
the  resisting  powers  of  all  the  body  tissues  is  the  inevitable  result.  As 
I  have  already  said,  such  supreme  importance  do  I  now  attach  to  the 
presence  of  pyorrhoea  alveolaris  in  sufferers  from  respiratory  disorders, 
that  should  a  patient  refuse  first  to  have  this  condition  adequately 
treated  by  a  thoroughly  competent  dentist,  then  I  firmly  and  finally 
refuse  to  undertake  the  treatment  of  the  respiratory  affection. 

These  preliminaries  having  been  arranged,  it  now  behoves  us  to  con- 
sider in  what  other  ways  the  defensive  mechanisms  of  the  body  can  be 
aided. 

The  mechanical  removal  of  the  bacteria  by  means  of  the  mucus 


62  THE    BACTERIAL    DISEASES    OE    RESPIRATION. 

can  be  assisted  by  the  careful  use,  night  and  morning,  of  the  nasal 
douche ;  to  the  precautions  necessary  in  its  use  I  have  already  alluded 
on  p.  50.  The  most  suitable  liquid  by  far  of  which  I  have  made  trial 
is  glycothymoline  i  part,  warm  water  3-5  parts  ;  not  only  is  this 
quite  unirritating  and  pleasant  to  use,  but  its  solvent  action  on 
mucus  is  particularly  good.  Hygienic  individuals  are  careful  to  bathe, 
to  wash  their  hands  and  face,  and  clean  their  teeth,  but  the  nasal 
cavities  with  the  accumulated  dust  and  dirt  and  bacteria  of  the  day 
they  are  wont  entirely  to  neglect.  The  careful  use  of  the  nasal  douche 
night  and  morning  is  therefore  much  to  be  recommended.  When  the 
nasal  mucosa  is  chronically  inflamed  and  over-dry,  as  in  atrophic 
rhinitis,  the  use  of  a  mildly  antiseptic  but  soothing  oily  spray  in  an 
efficient  nebuliser  is  also  advisable. 

The  following  prescription  may  prove  of  use  : 
R     Menthol  .         .         .         .         .         .         .     gr.  xx 

Camphor        .         .         .         .         .         .         .     gr.  xx 

Cinnamon  oil  ......     n\v 

Parolein  ad 5J 

When  follicular  tonsillitis  does  not  prove  to  be  entirely  amenable 
to  surgical  measures,  careful  painting  of  the  parts  twice  or  thrice  daily 
with  a  solution  of  i  part  of  chinosol  in  200  to  300  parts  of  glycerine  by 
means  of  a  fine  camel's  hair  brush  may  prove  of  service — for  this  hint  I 
am  indebted  to  my  friend  Mr.  F.  J.  Steward — while  sucking  formamint 
lozenges  also  aids  in  reducing  the  bacterial  content. 

Where  accumulations  of  pus  are  present,  as  in  infections  of  the 
accessory  sinuses,  it  is  obviously  necessary  that  these  be  removed 
either  by  lavage,  as  in  acute  sinusitis,  or  by  a  surgical  operation  to 
establish  free  drainage,  as  in  chronic  sinus  infections  which  refuse  to 
yield  to  lavage. 

It  is  beyond  the  scope  of  this  paper  to  go  further  into  the  treatment 
of  the  various  local  conditions  which  may  complicate  a  more  general 
respiratory  disorder ;  it  only  remains  to  say  that  the  careful  attention 
to  all  abnormalities  may  determine  the  final  success  of  any  more  general 
form  of  treatment  as  by  means  of  vaccines. 

Assuming,  then,  that  due  regard  has  been  paid  to  all  preliminaries, 
we  may  proceed  to  the  consideration  of  vaccine  treatment,  its  rationale 
and  method  of  employment.  Vaccine  therapy  depends  upon  this 
principle  :  "  That  the  animal  organism  is  capable  of  elaborating  anti- 
bodies to  any  foreign  albuminous  substance  introduced  into  it,  which  is 
soluble  in  the  tissue  fluids,  and  does  so  to  an  amount  which  is  in  excess 
of  that  required  to  neutralise  the  quantity  of  foreign  matter  introduced." 

Now  bacteria  are  foreign  albuminous  substances,  and  the  question  at 
once  occurs — Why,  if  this  principle  be  true,  does  the  body  not  conform 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  63 

to  it  by  manufacturing  more  than  sufficient  antibodies  to  the  bacteria 
to  neutraHse  them  and  so  put  an  end  to  the  infection  ?  The  answer  to 
this  is  that  in  the  great  majority  of  instances  it  does  so  do;  that  when 
it  fails  several  factors  may  conspire  to  hinder  its  good  work,  such  as  the 
following  : 

(i)  The  bacteria  may  be  introduced  in  such  numbers  that  the 
immunising  machinery  may  be  paralysed  locally  or  generally. 

(2)  That  when  this  paralysis  is  local  other  regions  of  the  body 
which  may  be  more  than  capable  of  making  good  the  local  defect  in 
production  of  antibodies  are  incapacitated  from  so  doing  by  lack  of  the 
necessar)'  stimulus,  viz.  the  bacteria  are  not  present  there  to  give  the 
stimulus. 

(3)  A  more  than  adequate  supply  of  antibodies  may  be  formed  in  the 
body  generally,  but  may  not  reach  the  areas  where  they  are  required 
owing  to  coagulation  of  sero-albuminous  exudate  or  formation  of 
thickened  walls  around  the  infected  foci. 

(4)  Certain  strains  of  bacteria  seem  to  be  incapable  of  exciting  the 
formation  of  immune  bodies  ;  this  would  seem  to  be  the  case  especialh- 
when  their  virulence  is  low. 

(5)  The  tissues  infected  may  be  ones  incapable  of  forming  immune 
bodies  altogether  or  only  in  very  small  quantities ;  this  may,  perhaps, 
be  the  case  with  the  superficial  layers  of  the  epidermis.  It  is  hard  to 
see  how  bacteria  infecting  the  most  superficial  layer  or  layers  of  the 
skin,  the  sweat,  sebaceous  and  mucous  glands  can  excite  the  pro- 
duction of  antibodies ;  toxins  maj^  perhaps  be  absorbed,  and  anti- 
toxins elaborated,  but  unless  the  bacteria  themselves  penetrate  the 
deeper  layers,  anti-bacterial  bodies,  such  as  opsonins,  lysins,  agglu- 
tinins, can  hardly  be  formed.  It  will  be  urged  that  in  such  instances 
the  bacteria  are  maintaining  a  merely  saprophytic  existence  ;  this  is 
more  or  less  true,  but  none  the  less  I  would  maintain  that  they  may  be 
provocative  of  conditions  unpleasant  to  the  host,  such  as  the  formation 
of  excessive  secretion  in  the  nasal  or  urethral  passages. 

(6)  There  may  be  defective  power,  either  congenital  or  acquired,  on 
the  part  of  the  tissues  generally  in  responding  to  bacterial  invasion  b}- 
the  elaboration  of  antibodies.  This  I  believe  to  be  a  more  common 
phenomenon  than  is  usually  considered  to  be  the  case,  and  to  afford 
explanation  of  some  of  the  failures  experienced  in  vaccine  treatment. 

Let  us  consider  how  these  various  obstacles  to  the  establishment  of 
immunity  may  be  overcome. 

(i)  When  the  paralysis  of  the  immunising  machinery  is  general, 
the  only  hope  would  appear  to  lie  in  the  administration,  best  locally 
into  the  infected  areas,  of  sera,  which  should,  if  possible,  possess  both 
antitoxic  and  bactericidal  properties.     Unfortunately,  ideal  sera  have 


64  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

not  yet  been  found  capable  of  production.  Anti-diphtheritic  serum  is 
antitoxic  but  not  bactericidal ;  anti-streptococcal  serum  appears  to  be 
bactericidal  rather  than  antitoxic  ;  anti-cholera  serum  is  only  lytic  ; 
the  anti-meningococcic  serum  of  Flexner  appears  to  be  both  bacterio- 
lytic and  antitoxic,  but  is  not  yet  an  ideal  serum. 

(2)  When  the  paralysis  of  the  immunising  machinery  is  purely 
local,  the  production  of  antibodies  may  be  incited  by  the  introduction 
into  healthy  tissues  of  the  suitable  corresponding  vaccine. 

(3)  The  supply  of  antibodies  in  the  body  generally  being  sufficient, 
local  deficiency  is  to  be  obviated  in  the  various  ways  which  Sir 
Almroth  Wright  has  so  carefully  indicated,  viz.  abscesses  may  be 
opened,  the  thickened  walls  scraped,  and  the  abscess  cavity  packed 
with  citrated  salt  solution,  the  citrate  decalcifying  and  so  preventing 
the  coagulation  of  the  lymph,  the  salt  increasing  osmosis  through  the 
infected  tissues ;  the  coagulability  of  the  blood  generally  may  be 
reduced  by  large  doses  of  citric  acid,  hypersemia  of  infected  areas  may 
be  brought  about  by  local  applications  of  heat  or  by  passive  congestion 
(Bier's  method). 

(4)  Diminished  power  of  exciting  antibody  formation  on  the  part  of 
the  infecting  bacteria  may  sometimes  be  obviated  by  the  introduction 
into  the  tissues  of  a  heterologous  vaccine  of  proved  efficiency. 
Instances  of  this  are  chronic  endocardial  infections  by  the  gonococcus 
and  B.  influenzcB,  some  long-standing  local  infections  by  the  gonococcus 
and  possibly  by  the  streptococcus. 

(5)  This  class  of  infection  is  one  to  which  local  antiseptic  treatment 
would  appear  to  be  applicable  rather  than  vaccine  therapy,  and  so,  in 
fact,  it  usually  is.  At  the  same  time  I  have  seen  instances  in  which 
careful  and  persistent  local  antiseptic  treatment  has  failed  yield  well 
when  vaccine  treatment  was  combined  with  the  former. 

(6)  remains  one  of  the  problems  for  future  studies  in  immunity  to 
solve ;  it  is,  I  believe,  only  an  exaggerated  form  of  the  failures  on  the 
part  of  the  tissues  to  establish  local  immunity.  My  own  feeling  is  that 
■our  present  knowledge  of  immunity  is  fragmentary  in  the  extreme,  and 
that  nothing  that  we  know  at  present  suffices  to  explain  why  one 
individual  should  throughout  life  be  susceptible  above  his  fellows  to  the 
attacks  of  the  staphylococcus  and  another  individual  be  apparently 
immune  against  the  staphylococcus,  but  fall  a  ready  victim  to  the 
bacillus  of  tuberculosis.  The  chemical  composition  of  the  tissues  as 
determined  probably  by  metabolic  processes  is  much  more  intimately 
concerned  in  immunity  than  is  at  present  realised.  Just  as  one  field 
will  grow  good  wheat  but  not  good  potatoes,  and  another  field  good 
potatoes  but  bad  wheat,  so  with  the  tissues  of  the  human  race  ;  lysins, 
opsonins,  agglutinins,  and  all  the  other  known  immune  bodies  are  but 


THE    BACTERIAL    DISEASES    OE    RESPIRATION.  65 

barriers  raised  against  bacteria,  whicli  are  already  present  and  in  pro- 
cess of  multiplication.  True  immunity,  I  feel  sure,  does  not  depend  on 
these,  but  on  some  as  yet  quite  unknown  conditions  which  render  the 
tissues  unsuited  to  the  very  existence  of,  or  rather  unattackable  by,  an 
invader.  To  make  my  meaning  clearer,  our  tissues  are  an  island  pro- 
tected by  a  fleet ;  it  is  upon  our  fleet  that  we  depend  for  our  existence, 
not  upon  the  land  soldiers,  which  merely  form  a  second  line  of  defence 
to  the  fleet.  Opsonins,  lysins,  and  agglutinins  are  but  land  soldiers  ; 
of  our  fleet  we  as  yet  know  nothing,  and  our  imperfect  efforts  are  per- 
force directed  to  the  strengthening  of  our  land  forces. 

The  Control  of  Dosage  and  Intervals. 

As  our  main  consideration  is  the  strengthening  of  the  defences 
by  the  aid  of  therapeutic  inoculations,  it  is  obviously  necessary  to 
'discuss  the  means  whereby  determination  may  be  made  of  the 
appropriate  times  and  degrees  of  the  augmentation,  or  in  other  words 
of  ascertaining  appropriate  intervals  and  dosages.  That  opsonic  index 
■determinations  have  taught  most  of  what  we  know  in  regard  to  the 
conduct  of  therapeutic  immunisation  will  be  readily  granted,  and  it  is 
therefore  with  some  hesitation  that  advocacy  is  made  of  other  methods 
of  control. 

The  bacterial  diseases  of  the  respiratory  tract  may  be  divided  into 
two  categories  :  (1)  Those  in  which  at  some  part  of  their  course,  usually 
at  the  beginning  of  the  attack,  the  bacteria  circulate  in  the  blood- 
stream, viz.  pulmonary  tuberculosis,  pneumonia,  and  sometimes,  at  all 
events,  true  influenza.  (2)  Those  in  w^hich  the  bacteria  throughout 
the  course  of  the  attack  are  localised  more  or  less  entirely  in  the 
•epithelial  and  endothelial  cells,  and  in  the  tissues  in  immediate 
juxtaposition  to  these  ;  instances  of  this  are  infections  of  the  nasal 
and  pharyngeal  mucosa  by  the  B.  septus,  of  the  laryngeal  and 
bronchial  mucosa  by  the  .V.  catarrhalis  or  Streptococcus  maxiums. 

Constitutional  symptoms,  when  present,  must  here  be  due  to 
absorption  of  toxins,  either  excreted  by  the  bacilli  or  the  result  of 
tissue  degeneration.  Such  immunity  curves  as  research  has  been 
able  to  evolve  pursue  more  or  less  constant  courses  in  both  classes 
■of  infection,  and  are  determined  b\'  (i)  the  responsive  powers  of  the 
individual  to  an  immunising  stimulus,  and  (2}  the  force  of  the  im- 
munising stimulus.  The  observations  by  G.  G.  MacDonald  (vide 
Studies  in  Pathology,  edited  by  W.  Bullock)  ;  by  Eyre  [Vaccines  and 
Sera),  and  by  Giglioli  and  Stradotti  {Interno  alle  Modificazione  dell' 
indice  opsonico  nel  corso  di  alcune  vialattie  acuta  da  infezione),  who 
especially  studied  and  correlated  the  tem.perature  and  opsonic  index 
•curves    in    various    cases    of   pneumonia    and    other    acute  infections 

5 


66 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


show  that  in  practically  all  instances  at  the  beginning  of  infection  the 
opsonic  index  is  low  (o"4-o'8)  and  temperature  considerably  above 
normal.  Should  the  disease  run  a  favourable  course  it  is  found 
that  at  the  onset  of  resolution  there  is  a  sudden  and  abrupt  rise  in 
the  opsonic  index  and  in  the  number  of  leucocytes  and  a  corresponding 
fall  in  temperature  (see  Chart  I),  whereas  in  those  cases  which  run  a 
fatal  course  the  opsonic  index  is  persistently  low,  and  the  temperature 
continues  pyrexial  in  type  until  near  the  end. 

In  the  former  class  of  case  the  tissues  have  succeeded  in  elaboratmg 
an  adequate  supply  of  antibodies,  antagonistic  to  the  pneumococci  and 

Chart  I. 


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Relation  between  Leucocytes,  Opsonic  Index  and  Temperature  in    a   Case 

OF  Pneumonia  (Eyre). 
Dotted  line  =  number  of  leucocytes  per  cubic  millimetre;  thick  line  =  opsonic  index  ; 

thin  line  =  temperature. 

their  products  ;  in  the  latter  class  of  case  the  tissues  are  unable  to 
respond  to  the  stimulus,  either  from  an  intrinsic  defect  or  from  the 
fact  that  the  stimulus  was  excessive  and  paralysing  in  its  effect,  and 
the  supply  of  antibodies  is  therefore  inadequate  to  cope  with  the 
invaders  and  their  toxins.  In  the  localised  infections,  such  as  nasal 
and  bronchial  catarrh  set  up  by  the  B.  septus  and  M.  catarrJialis  respec- 
tively, Benham  and  myself  have  observed  that  the  index  to  these 
organisms  is  usually  low  at  the  onset  of  the  attack  and  rises  rapidly  as 
convalescence  occurs,  whereas  chronicity  is  as  a  rule  synonymous  with 
persistence  of  a  subnormal  index. 

Since  it  appears,  then,  that  the  opsonic  index  gives  a  very  good  idea 
of  the  progress  of  the  case  in  catarrhal  disease  of  the  respiratory  tract,  it 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


6/ 


may  well  be  asked — Why  seek  other  methods  of  controllin,£^  dosage  and 
intervals  ?  The  answer  to  this  is  that  index  determinations  are  tedious 
and  troublesome  to  the  medical  man,  and  especiallv  is  this  the  case 
when  certain  strains  of  M.  catarrhalis  and  pneumococcus  have  to  be 
employed,  and  much  more  expensive  to  the  patient  than  most  can 
afford  in  these  or  any  other  times.  The  accuracy  of  index  determina- 
tions, again,  cannot  always  be  relied  upon,  nor  do  they  always  give 
a  true  picture  of  the  progress  of  the  case  :  a  high  index  especiallv  does 
not  always  indicate  progress,  though  a  low  index  does  usuallv  connote 
a  failure  to  improve  on  the  part  of  the  patient.  Let  us,  then,  consider 
what  other  guides  we  can  substitute  for  the  opsonic  index. 

(i)   In  such  cases  as  exhibit  pyrexia  we  have   seen   that  index  and 
temperature  run  an  inverse  course  to   each   other,  so  that  despite  the 

Chart  II. 


fact  that  temperature  is  considered  to  be  a  measure,  not  of  immunising 
response,  but  of  toxaemia,  the  curve  may  receive  the  following  interpreta- 
tion : 

A  rising  temperature  indicates  increasing  toxaemia  and  a  faUing 
opsonic  index  ;  if  the  tissues  be  capable  of  adequate  response  to  the 
various  stimuli,  a  subsequent  fall  in  the  curve  will  indicate  diminishing 
toxcemia  and  rising  index.  This,  moreover,  is  but  a  partial  statement 
of  the  truth,  and  I  cannot  but  feel  that  far  too  much  stress  has  been 
laid  on  the  temperature  curve  as  a  measure  of  the  toxaemia.  The 
temperature  curve  is  much  more  than  a  measure  of  the  toxsemia :  it  is 
compounded  of  many  factors,  one  of  which  is  the  stimulus  to  the  forma- 
tion of  various  immune  bodies.  The  toxa;mic  effect  of  a  dose  of  half 
a  million  B.  typhosus  in  the  form  of  a  vaccine  must  be  practicallv 
negligible ;  none  the  less  such  an  administration  mav  be  followed  bv 
a  rise  of  temperature  of  4,°-f  F.  (see  Chart  II-j.  Even  granting  that 
the  body  cells  of  this  case  were  hypersensitive  to  the  typhoid  toxin,  the 

*  Reproduced  from  vol.  i,  No.  i,  Journal  of  Vaccine  Therapy,  after  Dr.  Wallis. 


68 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


pyrogenic  effect  can  hardly  be  interpreted  as  due  solely  to  the  poisoning 
action  of  the  bacterial  toxins  in  the  vaccine  upon  these  cells  ;  rather 
was  it  due  to  the  stimulating  effect  upon  the  metabolic  processes  of 
the  cells  whereby  antibodies  are  generated.  The  curve  of  antibody 
formation  will  therefore  lag  somewhat  behind  the  temperature  curve, 
the  result  being  that  with  an  effective  stimulus  the  temperature  will 
have  already  fallen  by  the  time  that  the  antibody  curve  has  risen 
to  an  appreciable  extent.  The  pulse-rate  I  take  to  be  more  nearly 
a  guide  to  the  toxeemic  effect  of  the  infection  upon  the  tissues  generally 
and  the  higher  nerve  centres  in  particular,  but  it,  too,  affords  a  rough 
measure  of  the  immunising  effect.  It  is  quite  rare  to  find  a  dose  of 
vaccine  producing  any  local  effect  upon  a  lesion  which  has  not  resulted 


Chart  III. 


Chart  IV. 


Charts  Illustrating    Rise    in   Temperature,  Pulse-Rate   and    Opsonic    Index 
AFTER  Therapeutic  Doses  of  Tuberculin   (Ian  Struthers  Stewart). 

in  a  prior  acceleration  of  the  pulse-rate.  In  short,  the  usual  result  of 
a  therapeutic  inoculation  is  to  produce  a  slight  rise  of  temperature  and 
an  accelerated  pulse-rate  succeeded  by  a  diminution  in  these  and  a  rise 
in  the  curve  of  opsonin  and  such  other  immune  bodies  as  it  is  at 
present  possible  to  measure  (see  Charts  III  and  IV). 

(2)  The  rise  in  temperature  and  acceleration  in  pulse-rate  may  be 
accompanied  by  a  slight  feeling  of  malaise  and  mild  headache,  which 
in  turn  are  succeeded  by  a  feeling  of  increased  general  well-being  and 
improved  appetite ;  the  former  symptoms  correspond  to  a  lowered 
resistance,  the  latter  to  an  increased  production  of  the  immune  bodies. 

(3)  The  effect  upon  a  local  lesion  is  the  production  of  hyperasmia  in 
and  around  it,  the  immediate  result  of  this  being,  perhaps,  slight 
increase  of  pain  and  of  secretion  or  discharge.  This  increased  blood 
supply  is  especially  easy  to  observe  directly  in  the  case  of  such  lesions 
as  tuberculosis  of  the  iris  and  larynx,  lupus,   and  furunculosis.     In 


THE    P5ACTERIAL    DISEASES    OF    RESPIRATION.  69 

catarrhal  affections  of  the  respiratory  tract  there  ma\-  be  a  temporarv 
increase  of  cough  and  secretion  ;  the  latter  may  be  measured,  and 
stethoscopic  examination  of  the  chest  will  reveal  moist  sounds  where 
none  before  existed,  or  increased  moist  sounds  where  these  were 
already  present  :  dry  sounds,  likewise,  may  be  caused  to  appear  or 
increased  in  number  and  in  volume.  Subsequently  the  inverse  change 
will  take  place  in  regard  to  all  these.  There  will  thus  be  an  alteration 
produced  in  the  character  both  of  the  fluid  and  cellular  constituents  of 
the  secretions.  How  these  observations  may  be  utilised  in  controUing 
the  course  of  therapeutic  immunisation  will  be  fullv  dealt  with  later 
(see  pp.  91-95  and  Charts  \'-XI). 

(4)  A  change  may  also  be  observed  in  the  bacterial  contents  of  the 
secretion  and  in  the  phagocytic  powers  of  the  cells.  The  bacteria  mav 
be  diminished  in  actual  numbers,  found  of  diminished  power  of  growth 
in  culture,  or  be  seen  agglutinated  together  or  undergoing  lysis,  whilst 
phagocytosis  may  be  found  to  be  active  where  previously  it  was  non- 
existent. 

(5)  As  immunisation  is  conducted  to  a  successful  issue,  the  patient 
may  experience  an  increased  sense  of  well-being,  gain  appetite  and 
weight,  experience  less  discomfort  from  the  symptoms,  and  exhibit  an 
obvious  improvement  in  the  state  of  all  the  tissues. 

(6)  The  reaction  of  the  tissues  in  immediate  proximity  to  the  site 
of  inoculation  is  held  by  some  to  be  a  m.easure  of  the  immunising 
response  ;  this  is  to  some  extent  the  case,  but  so  many  complicating 
factors  are  concerned  that  in  the  majority  of  instances  I  think  it  should 
be  neglected.  The  nature,  mode  of  preparation  and  volume  of  the 
inoculum,  the  amount  and  nature  of  the  antiseptic  contained  therein, 
the  density  or  laxity  of  the  tissues  into  which  the  inoculum  is  intro- 
duced, all  influence  the  degree  of  local  reaction.  The  vaccines  of  some 
bacteria  always  produce  a  marked  local  reaction  ;  some  are  more  toxic 
if  heated  during  manufacture,  others  less  so  :  a  large  volume  of  diluting 
fluid  and  high  percentage  of  antiseptic  increase  the  local  reaction, 
whilst  the  introduction  of  the  inoculum  into  scanty  subcutaneous  tissues 
or  just  beneath  a  layer  of  fascia  is  sure  to  be  provocative  of  more 
reaction  than  if  the  inoculation  be  done  into  abundant  subcutaneous 
tissue  or  muscle  substance. 

In  view  of  the  frequency  with  which  I  am  asked  the  question, 
"What  constitutes  a  reaction  to  a  therapeutic  inoculation  ?  ""  the 
following  table  may  prove  of  service  : 

Table  of  Reactions  Indicative  of  Ejficient,  hut  not  Excessive  Dosage. 
I.  Slight  temporary  fall  in  opsonic  index  succeeded  bj-  a  more  marked 

and  more  permanent  rise. 


70  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

2.  Rise  in  the  curve  of  agglutinins,  lysins,  etc.,  which  may  be  preceded 

by  a  slight  temporary  fall. 

3.  Rise  in  temperature  of  i°-i'5°  F.,  or  in  pulse-rate  of  10-20  beats, 

followed  within  twenty-four  hours  by  a  fall,  and  steadying  of  the 
same  at  a  more  satisfactory  level. 

4.  SHght  feeling  of  malaise  or  headache,  passing  off  within  eighteen 

hours,  and  succeeded  by  a  feeling  of  increased  well-being  and 
better  appetite. 

5.  Increased  hypersemia  around  the  lesions,  with  resultant  increase  of 

pain  and  in  the  amount  of  secretion,  passing  off  in  twelve  to 
twenty-four  hours,  and  being  succeeded  by  increased  comfort  and 
diminished  secretion.  The  amount  of  secretion  may  be  measured, 
or  its  presence  estimated  by  stethoscopic  examinations.  The 
swelling  and  reddening  of  the  local  lesions  are  succeeded  by 
diminution  in  size  and  a  more  healthy  appearance. 

6.  Improvement  in   the   nature   and   degree  of  the    bacterial    content 

of  the   secretion  and   impairment  of  their  vitality  as  observed  in 

cultural  experiments. 
From  this  it  will  readily  be  understood  that  a  marked  and  prolonged 
fall  in  opsonic  index,  or  in  the  amount  of  lysins  or  agglutinins,  a  rise 
of  temperature  of  2°  F.  or  of  pulse-rate  by  20  beats,  which  fails  to  fall 
within  twenty-four  hours  to  a  level  lower  than  that  previously  existent, 
pronounced  headache,  malaise  or  vomiting,  aggravation  of  local 
symptoms  which  is  not  speedily  converted  into  an  amelioration,  or 
impairment  of  the  patient's  general  condition  are  each  and  sundry 
indicative  of  excessive  dosage.  On  the  other  hand,  the  failure 
to  produce  any  apparently  unfavourable  or  unpleasant  prelude  to  an 
immediate  improvement  is  indicative,  as  a  rule,  of  a  dosage  too  small 
to  produce  other  than  a  very  temporary  good  effect.  At  times  the 
patient's  condition  may  be  such  that  any  stimulus  other  than  a  minimal 
one  cannot  be  applied  without  some  risk ;  such  cases,  however,  are 
relatively  few,  and  as  experience  accumulates  the  fact  becomes  in- 
creasingly clearer  that  minimal  stimuli  applied  at  infrequent  intervals 
are  apt  to  produce  a  condition  of  anaphylaxis  or  hypersensitiveness,  so 
that  toleration  to  higher  dosages  and  a  high  degree  of  immunity 
become  difficult  to  obtain.  Dosages,  on  the  other  hand,  productive  of 
moderate  reactions  and  repeated  at  not  too  infrequent  intervals  are 
devoid  of  risk,  and  by  their  aid  a  high  degree  of  immunity  can  be  the 
more  speedily  established,  provided,  that  is,  that  the  tissues  are  capable 
of  response  to  such  stimuli.  The  importance  of  this  point  I  shall 
explain  more  thoroughly  in  the  section  devoted  to  the  vaccine  therapy 
of  pulmonary  tuberculosis. 

Finally,  attention  may  be  drawn  to  the  following  points  in  dosage  : 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  7 1 

(i)  That  when  a  vaccine  has  been  prepared  some  time  the  bacteria 
necessarily  will  sink  to  the  lowest  level  of  the  bulb,  and  if  the  contents 
be  not  thoroughly  shaken  a  mere  fraction  of  the  bacteria  may  be  with- 
drawn from  the  bulb  and  introduced  into  the  patient,  who  thus  receives 
a  much  smaller  dosage  than  was  intended. 

(2)  That  so  long  as  a  given  dosage  produces  adequate  reaction  and 
subsequently  an  improvement  in  the  condition  any  increase  is  not  advis- 
able ;  unnecessary  increase  of  dosage  cannot  be  too  strongly  deprecated. 

IV   (6)    Special  Considerations  in  the    Conduct  of  Vaccine  Treatment  of 

Respiratory    Catarrhs. 

It  was  in  May,  1904,  that  I  performed  upon  myself  the  first  admini- 
stration of  a  vaccine  for  the  cure  of  chronic  respiratory  catarrh  ;  since 
that  time  vaccine  treatment  has  been  extended  more  freely  in  the 
direction  of  catarrhal  disorders  of  the  respijatory  tract  than  perhaps 
in  any  other,  and  judging  from  such  reports  as  have  been  published  or 
have  reached  me  privately  I  think  it  may  be  safely  said  that  in  no 
other  disorders  are  such  uniformly  successful  results  achieved. 

In  the  lirst  part  of  this  chaper  I  have  dealt  with  the  preliminary 
considerations  that  must  be  kept  in  mind  before  vaccine  treatment 
is  to  be  begun.  In  the  event  of  a  sufferer  seeking  relief  from  an 
acute  attack  of  nasal  catarrh  or  laryngitis  it  is  obviously  difficult  to 
postpone  special  treatment  for  that  attack  until  such  time  as  due 
attention  has  been  paid  to  any  abnormalities  ;  none  the  less,  proper 
counsels  should  not  be  deferred,  and  if  the  attacks  be  not  of  undue 
severity,  I  endeavour  to  prevail  upon  the  patient  to  employ  more 
stereotyped  and  general  treatment  during  that  attack,  then  to  have 
abnormalities  treated  and  finally  to  return  for  imm.unisation.  \\^ith 
chronic  infections  the  necessary  preliminaries  should  be  insisted  on  as 
I  have  already  said.  Should  no  abnormal  conditions  be  existent  or  should 
they  have  been  already  put  to  rights  our  procedure  should  be  as  follows  : 

(i)  By  means  of  suitable  questions  endeavour  is  made  to  deter- 
mine whether  the  attacks  from  which  the  patient  suffers  are  always 
due  to  the  same  micro-organism  or  micro-organisms.  How  this  is 
done  I  have  already  partly  indicated  in  the  issues  of  the  Lancet  for 
November  28th  and  December  5th,  igo8,  and  February  13th,  igog. 
The  most  characteristic  effects  of  infection  by  each  catarrhal  organism 
briefly  are  as  follows  : 

(i)  That  by  the  B.  septus  usually  begins  as  dryness  or  tickling  of 
the  soft  palate,  the  inflammatory  condition  extending  within  twenty- 
four  hours  to  the  nasal  mucosa  so  that  sneezing  and  discharge  of  thin 
nasal  mucus  result,  and  to  the  pharynx,  so  that  there  is  some  pain  in 


72  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

swallowing.  As  the  infection  practically  never  extends  to  the  larynx 
and  lower  respiratory  passages,  cough,  other  than  pharyngeal,  is  not 
present,  and  expectoration  scanty ;  as  the  Eustachian  tube  appears 
but  rarely  to  be  involved  deafness  and  noises  in  the  ear  are  not 
produced  ;  as  the  accessory  air-cells  as  a  rule  escape  attack,  sense  of 
fulness  and  referred  head-pains  are  also  absent.  I  think  the  antrum  does 
frequently  become  involved,  but  the  process  is  a  mild  one,  produces 
little  or  no  symptoms  and  rapidly  clears  up ;  on  the  other  hand,  as  the 
nasal  mucosa  bears  the  brunt  of  the  attack,  sneezing,  copious 
discharge,  considerable  swelling  of  the  tissues,  loss  of  smell  and  taste 
are  the  prominent  features  ;  toxic  absorption  being  slight,  headache, 
malaise  and  pyrexia  are  also  slight.  After  three  or  four  daj^s  the  acute 
stage  rapidly  subsides,  and  a  subacute  stage,  characterised  by  thick  but 
not  very  purulent  mucus,  persists  for  perhaps  an  equal  period.  True 
chronic  infection  of  these  parts  by  the  B.  sephLs  is  quite  rare ;  when  it 
does  exists  it  is  revealed, rather  by  a  bacteriological  examination  and 
the  recurrence  of  acute  attacks  than  by  any  chronic  symptoms. 

(ii)  The  Micrococcus  catarrhalis,  on  the  other  hand,  may  initiate  its 
attack  at  any  part  of  the  respirator}-  tract  and  so  produce  anything 
from  a  purely  nasal  catarrh  to  a  capillary-  bronchitis.  Characteristi- 
cally I  think  it  begins  with  an  inflamed  feeling  of  the  fauces  and  naso- 
pharynx ;  extension  into  the  nose  and  larynx  soon  ensues,  so  that  there 
is  profuse  thin  discharge  from  the  former  and  expectoration  of  thin, 
colourless,  rather  watery  mucus  from  the  latter ;  impairment  of  voice, 
cough,  and  sore  feeling  in  the  trachea  are  necessary  accompaniments, 
the  Eustachian  tube  becomes  frequently  involved,  so  that  some  deafness 
and  noises  in  the  auditory  passages  result.  Infection  of  the  accessory 
sinuses  is  the  rule  rather  than  the  exception,  so  that  sense  of  fulness 
and  perhaps  referred  pains  may  be  felt;  toxic  absorption  produces 
headache,  malaise  and  some  rise  of  temperarure  ;  while  erythema  and 
petechise  have  been  also  noted.  At  the  end  of  three  to  four  days  the 
subchronic  stage  is  entered  on  by  the  infection  in  the  nasal  passages 
and  may  persist  for  weeks  so  that  profuse  muco-purulent  mucus  may 
be  frequently  expelled ;  at  the  same  time  the  lower  respiratory 
passages  may  be  in  turn  involved,  with  the  final  production  of  a 
troublesome  and  persistent  but  not  very  acute  infection  of  the  bronchi 
and  bronchioles  from  which  copious  thin,  not  very  tenacious  or 
purulent  mucus  is  voided. 

Infections  by  the  M.  catarrhalis  have  a  decided  tendency  either  to 
become  truly  chronic  or  to  frequently  recur.  At  times  they  very  closely 
simulate  infections  by  the  B.  influenzce. 

(iii)  The  Micrococcus  paratetragenus  may  behave  precisely  like  the 
M.  catarrhalis  ;  but  the  experience  gained  from  two  epidemics  seems  to 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  73 

indicate  that  the  lar3-nx  is  its  favourite  point  of  attack.  The  first  symptom 
may  be  huskiness  of  voice  followed  in  a  da}'  or  two  by  a  dry  paroxysmal 
cough,  which  may  result  in  the  expulsion  of  a  tiny  blob  of  clear  but 
exceedingly  tenacious  mucus  ;  subsequently  the  infection  may  extend 
simultaneously  into  the  upper  and  lower  passages.  Secretion  is  rarely 
profuse  and  practically  never  even  muco-purulent ;  involvement  of  the 
accessory  sinuses  I  have  never  seen.  Persistent  dry  hacking  cough  is 
its  main  characteristic. 

(iv)  The  bacillus  of  Friedlander  group. — This  organism  usually  confines 
its  attentions  to  the  nasal  passages  and  their  adnexa.  The  first 
symptoms  of  its  activity  are  sneezing,  some  malaise,  slight  headache 
and  loss  of  smell.  The  nasal  discharge  soon  becomes  exceedingly 
profuse  ;  usually  it  is  clear  and  colourless,  but  when  the  antrum  or 
sinuses  become  involved  it  takes  on  a  muco-purulent  character.  As  the 
Eustachian  tube  almost  always  escapes  attack  deafness  and  noises  are 
not  experienced ;  the  throat  does  not  become  inflamed,  nor  the 
larynx  and  trachea  involved ;  sore  throat  and  cough  are  therefore 
absent.  Rarely  in  the  adult,  but  more  commonly  in  the  child,  the 
bacillus  of  Friedlander  may  make  its  way  into  the  bronchi  or  pulmonary 
tissues,  setting  up  bronchitis  on  the  one  hand  and  broncho-pneumonia 
on  the  other.  It  is  the  variants  of  this  organism  which  more  often  set 
up  these  latter  conditions,  while  those  forms  which  resemble  it  ver}- 
closely,  except  that  they  possess  motility,  are  those  which  are  most 
prone  to  involve  the  Eustachian  tube  and  accessory  sinuses.  Infections 
by  the  bacillus  of  Friedlander  are  especially  apt  to  assume  chronicity. 

(v)  The  pneumococcus,  like  the  M.  catavrhalis,  is  capable  of  involving 
each  and  every  portion  of  the  respiratory  tract.  The  most  character- 
istic attack  begins  as  follows  :  For  a  day  or  two  there  is  a  feeling  in 
the  larynx  and  upper  trachea  as  if  sand-paper  had  been  applied  to  the 
mucous  membrane  ;  cough  is  very  harsh  and  dry  ;  convulsive  efforts  may 
finally  succeed  in  expelling  a  blob  of  mucus  very  similar  to  that  charac- 
teristic of  the  M.  paratetragemis  except  that  it  may  possess  a  yellowish 
tinge.  At  the  end  of  the  second  or  third  day  the  infection  has  begun 
to  spread  upwards  into  the  naso-pharynx  and  down  the  trachea,  so 
that  by  the  third  or  fourth  day  the  pharynx  and  trachea  may  feel  sore, 
while  expectoration  and  nasal  discharge  become  profuse  and  soon 
assume  a  muco-purulent,  and  later  a  purulent  yellow  look  and  possess 
slight  tenacity.  Toxic  absorption  may  produce  considerable  malaise  and 
headache  and  some  rise  of  temperature  ;  involvement  of  the  sinuses,  a 
sense  of  fulness  and  referred  head-pains ;  extension  to  the  chest,  moist 
sounds  in  the  bronchi  and  bronchioles,  and  muscular  or  pleuritic  pains 
are  common.  Finally,  the  alveoli  may  be  attacked  and  a  condition  of 
definite  pneumonia  established.  This  is  a  description  of  atypical  pneumo- 


74  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

coccal  invasion  of  the  respiratory  tract;  occasionally,  however,  the  nasal 
mucosa  is  the  lirst  attacked  ;  sometimes  it  is  the  bronchial  mucosa,  or 
yet  again  the  pulmonary  cells  ;  sometimes  the  attack  may  be  localised 
entirely  to  the  nasal  passages,  sometimes  entirely  to  the  passages  of  the 
chest — an  excellent  example  of  this  last  is  afforded  by  the  condition 
known  as  acute  suffocative  catarrh  of  Laennec. 

(vi)  The  B.  influenzce  produces  the  most  protean  symptoms,  but  it 
must  be  borne  in  mind  that  usually  associated  with  it  is  the  pneumo- 
coccus. 

An  attack  of  true  influenza  is  usually  ushered  in  by  extreme  malaise, 
headache,  joint  and  muscle  pains,  and  pyrexia,  perhaps  with  rigors. 
Before  any  respiratory  symptoms  have  developed  considerable  upset  of 
the  digestive  system  may  be  produced,  while  the  nerves  may  be  so 
involved  that  neuritis,  diffuse  or  local,  or  herpes  zoster  may  appear. 
In  such  instances  the  infection  is  probably  a  systemic  one,  subsequently 
to  be  localised  in  the  pulmonary  tissues. 

Sometimes  infection  is  confined  to  the  nasal  passages  and  their 
adnexa,  and  does  not  extend  to  the  lower  respiratory  tract  ;  in  these 
instances  infection  of  the  antrum,  of  the  ethmoidal,  frontal  and  sphe- 
noidal cells,  and  of  the  Eustachian  tube  is  very  common,  and  while  in 
the  majority  of  instances  chronic  infection  thereof  does  not  result,  in  a 
by  no  means  inconsiderable  number  chronicity  does  ensue. 

(vii)  The  streptococcus  group,  while  certainly  concerned  in  such  con- 
ditions as  chronic  post-nasal  catarrh,  bronchitis  and  asthma,  and  often 
in  infection  of  the  sinuses,  and  sometimes  in  the  later  stages  of  catarrhs 
of  the  upper  passages,  yet  produces  no  symptoms  which  enable  us  to 
fix  on  one  of  its  members  as  certainly  concerned  in  any  of  these  pro- 
cesses ;  to  bacteriological  research  must  be  left  the  determination  of 
this  question  in  any  given  case. 

Armed,  then,  with  the  knowledge  of  these  points  of  differential  dia- 
gnosis, it  becomes  a  relatively  easy  matter,  by  means  of  appropriate 
questions,  to  elicit  from  an  intelligent  patient  whether  all  attacks  of 
respiratory  catarrh  from  which  he  suffers  are  set  up  by  the  same 
organism  or  organisms  ;  for  it  is  the  rule,  rather  than  the  exception,  not 
only  that  susceptibility  to  several  catarrhal  organisms  should  exist,  but 
that  two  or  more  of  these  should  make  a  simultaneous  attack  ;  a  little 
practice  will  enable  one  not  only  to  say,  for  instance,  that  a  patient  is 
suffering  from  a  pure  B.  septus  infection,  but  that  there  is  a  combined  attack 
by  the  bacillus  of  Friedlander  and  M.  catarrhalis,  or  pneumococcus  and 
B.  influenza:.  But  it  may  be  said,  What  help  do  we  receive  from  this  more 
or  less  guess-work  diagnosis  ?  The  answer  is  this  :  Not  only  does  this 
guess-work  diagnosis  sometimes  prove  more  accurate  than  a  bacterio- 
logical  examination  of  the  secretions,  for  the  sample  taken  may  be 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  75 

ill-chosen,  or  the  true  infecting  organism  not  yet  be  in  process  of  free 
discharge  and  so  escape  detection  until  subsequent  examinations,  but 
it  also  enables  us  to  answer  the  question  every  patient  is  sure  to  put, 
"  Will  this  vaccine  not  only  help  to  free  me  from  the  present  attack  but 
.also  protect  me  from  future  ones  ?  "  Obviously  a  vaccine  made  during 
an  attack  due,  say,  to  the  pneumococcus  and  M.  catarrhalis,  will  in  no 
way  help  to  ward  off  subsequent  attacks  by  the  B.  septus  or  B.  influenza ; 
and  careful  investigation  on  the  lines  indicated  will  aid  in  the  determina- 
tion of  the  patient's  liability  to  subsequent  attacks  by  these  organisms. 
Personally,  if  I  decide  that  my  patient  is  liable  to  infection  by  organ- 
isms other  than  those  of  which  I  am  about  to  prepare  the  autogenous 
vaccine,  I  then  lay  before  him  these  alternatives  : 

(i)  To  include  with  his  autogenous  strains  heterologous  vaccines  of 
:such  other  catarrhal  organisms  as  he  appears  susceptible  to. 

(2)  To  confine  my  attention  for  the  time  being  to  the  preparation  of 
the  autogenous  vaccine  ;  to  inform  the  patient  that  inasmuch  as  this  will 
■only  protect  against  infection  by  the  contained  micro-organisms  he  will 
remain  susceptible  to  other  varieties,  and  in  the  event  of  being  attacked 
hy  these  it  will  be  necessary  for  him  to  return  and  afford  opportunity 
for  the  preparation  of  a  second  autogenous  vaccine  to  combine  with 
the  former. 

The  preparation  of  the  vaccine. —  Having  thus  made  a  tentative 
•diagnosis  and  decided  the  precise  object  that  it  is  desired  to  achieve, 
specimens  are  taken  with  the  precautions  indicated  on  pp.  8-10. 
Smears  are  prepared,  stained,  and  examined  by  the  methods  already 
■outlined  for  bacteria  and  cellular  contents,  while  cultures  are  made  on 
the  various  media  indicated  by  this  preliminary  examination.  After 
adequate  incubation  at  37°  C,  it  may  be  for  one,  two,  or  three  days, 
•colonies  of  the  various  organisms  of  which  it  is  desired  to  prepare 
vaccines  are  picked  off  and  inseminated  upon  fresh  culture-plates  in 
order  to  secure  pure  cultures.  Here  let  me  just  mention  that  inas- 
much as  great  difficulty  sometimes  presents  itself  in  the  growth  of 
:Some  organisms  such  as  the  B.  influenzce  in  subculture,  that  it  may 
be  requisite  to  employ  special  enrichment  of  the  culture  media  (p.  32), 
and  in  addition  to  retain  the  original  culture  -  plates  until  it 
may  be  seen  whether  growth  will  or  will  not  then  take  place  ;  in  the 
latter  event  the  original  plates  must  be  employed  for  the  preparation 
of  the  vaccine  of  the  delicately  growing  micro-organism  ;  as  a  rule 
the  differential  standardisation  of  such  a  mixed  vaccine  presents 
few  difficulties,  and  various  little  devices  which  ingenuity  will  suggest 
may  be  employed  in  face  of  these.  Suppose,  for  instance,  that  it  be 
desired  to  prepare  vaccines  of  M.  catarrhalis  and  B.  influenzce,  and  that 
the  latter  has  refused  to  grow  in  subculture,  after  thirty-six  to  forty- 


^6  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

eight  hours'  incubation  of  the  original  plates  the  colonies  of  both 
organisms  will  have  well  developed.  Subcultures  are  taken  of  the 
M.  catarrhalis,  and  a  little  ot  per  cent,  aqueous  salt  solution  is  added 
to  the  growth  and  emulsification  performed  with  light  touches  of  a  bent 
glass  or  aluminium  rod  ;  the  growth  of  B.  influenzcF  will  be  readily 
detached,  whereas  the  M.  catarrhalis  will  adhere  to  the  medium  with 
considerable  tenacity  ;  the  colonies,  moreover,  even  if  some  do  become 
detached,  will  not  readily  disintegrate.  The  mixed  emulsion  is  then 
pipetted  off  and  centrifugalised  at  a  slow  rate ;  this  will  amply  suffice 
to  throw  down  the  great  bulk  of  the  M.  catarrhalis  and  leave  the 
B.  influensce  in  suspension.  The  emulsion  is  then  carefully  pipetted  off 
from  the  sediment  and  standardised  in  the  usual  manner  (Vaccine 
Therapy,  third  edition,  p.  40).  If,  in  addition,  a  vaccine  of  the  M. 
catarrhalis  be  desired  the  subcultures  are  to  be  employed.  As  I  have 
already  said,  emulsification  of  the  M.  catarrhalis,  and  sometimes 
of  the  M.  paratetragenus  and  certain  strains  of  streptococcus,  is 
by  no  means  easy  to  perform.  The  following  hints  may  prove 
of  service :  (r)  Make  the  culture  medium  rather  less  solid  than 
usual,  so  that  there  is  abundant  water  of  condensation  ;  (2) 
incubate  for  not  more  than  twelve  to  fifteen  hours ;  (3)  emulsify 
by  means  of  a  bent  aluminium  rod  which  has  been  slightly  roughened 
by  means  of  coarse  sand-paper  or  a  fine  file ;  (4)  do  not  add  further 
fluid  to  the  culture  plate  until  a  rough  emulsion  has  been  made 
in  the  water  of  condensation  ;  (5)  pipette  off  a  little  of  this  emulsion, 
and  place  in  a  strong  test-tube  with  eight  to  ten  glass  beads,  and  try 
whether  a  salt  solution  of  o"i  per  cent,  or  i*o  per  cent,  concentration 
aids  emulsification  ;  also  see  whether  heating  the  tube  and  contents  in 
a  water  bath  for  a  few  seconds  at  70°-y^°  C.  is  an  additional  help- 
Having  ascertained  the  conditions  which  most  favour  emulsification,. 
employ  these  in  the  treatment  of  the  remainder  of  the  thick  emulsion  ; 
dilute  the  product  with  salt  solution  of  the  appropriate  strength 
and  at  the  appropriate  temperature,  centrifuge  rapidly  for  a  few 
seconds,  pipette  off  the  upper  portion  and  immediately  standardise. 

Where  treatment  of  a  case  is  to  be  conducted  with  the  vaccines  of 
more  than  one  organism,  mixture  may  be  made  of  the  several  vaccines 
after  standardisation  in  the  desired  ratios;  the  bulk  of  the  inoculum,, 
and  so  the  amount  of  local  reaction,  is  thus  kept  at  a  minimum.  As 
regards  the  method  of  sterilising  the  vaccines,  it  may  be  said  that  the 
addition  of  o'3-o*4per  cent,  tricresol  to  many  vaccines  of  concentration 
of  not  more  than  2000  million  organisms  per  c.c.  will  secure  complete 
sterility  in  twenty-four  hours;  with  some  bacteria fthis  concentratiort 
may  be  greatly  exceeded ;  with  others  sterility  is  secured  only  with 
much  lower  concentrations. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  J "] 

In  this  wav  heating  of  the  vaccine  may  often  be  avoided,  but  it 
is  a  fact  that  occasionallv  a  vaccine  steriHsed  by  antiseptic  proves  to 
be  of  less  service  than  one  sterilised  by  moderate  heat  for  not  too  long 
a  time  :  this  especially  I  have  found  to  be  the  case  with  certain  strains 
of  pneumococcus  and  streptococcus ;  more  often  the  reverse  holds  good. 

If  heat  be  used  to  sterilise  the  vaccine  a  temperature  of  56°-5S°  C. 
for  thirty  to  forty-five  minutes  will  as  a  rule  suffice,  unless,  of  course, 
contamination  with  sporing  organisms  be  present ;  every  care  should 
be  taken  to  exclude  these,  but  should  any  find  their  way  into  the 
emulsion  from  the  air  or  in  the  diluting  fluid,  their  multiplication  may  be 
completely  inhibited  by  the  addition  of  0*3  per  cent,  tricresol  or  carbolic 
acid  to  the  emulsion.  Cultural  tests  should  always  be  performed  upon 
the  finished  product,  and  if  any  living  bacteria  are  detected  their  precise 
nature  must  be  determined  :  if  they  consist  of  an  organism  which  under 
any  conditions  is  capable  of  exerting  a  pathogenic  action,  the  vaccine 
must  of  course  be  discarded  and  a  fresh  one  prepared  ;  on  the  other  hand 
two  or  three  spores  oiB.  subtilis  or  B.  mesentericus  in  a  dose  of  vaccine 
are  quite  devoid  of  danger  ;  at  the  same  time  they  are  better  absent.  As 
a  rule  heating  the  vaccine  to  a  higher  temperature  than  that  indicated 
impairs  its  efficiency  and  keeping  properties,  and  increases  its  toxicity. 

Some  of  each  vaccine  in  the  highest  concentration  should  be  stored 
for  future  need,  for,  as  immunisation  proceeds,  some  organisms  may 
disappear  before  others,  and  the  administration  of  the  corresponding 
vaccine  be  unnecessary;  or,  again,  the  proportions  in  which  the 
several  have  been  blended  may  not  prove  to  be  the  best. 

The  administration  of  the  vaccine. — Vv'hile  it  is  the  general  consensus 
of  opinion  that  the  introduction  of  a  vaccine  directly  into  the  substance 
of  the  tissues  has  decided  advantages  over  oral  administration  as 
advocated  by  Latham,  yet  at  times  the  latter  procedure  would  seem  to 
offer  certain  advantages.  At  a  discussion  before  the  Therapeutical 
Section  of  the  Royal  Society  on  February  20th,  1912  wide  Proc.  Roy. 
Soc.  Med.,  March,  1912,  Ther.  Section,  p.  55),  Latham  outlined 
his  position  more  clearly,  and  removed  certain  misapprehensions.  He 
would  now  appear  to  uphold  this  procedure  only  when  there  are  definite 
obstacles  to  the  subcutaneous  administration,  and  strongly  urges  the 
necessity  of  giving  the  vaccine  upon  a  perfectly  empt}-  stomach  early 
in  the  morning,  and  in  a  liquid  isotonic  with  the  tissue  fluids  and  free 
from  all  antiseptics.  Stomach  derangements  or  a  furred  tongue  are 
contra-indications  to  the  procedure.  While  there  is  considerable 
difficulty  in  understanding  how  the  administration  by  the  mouth  of 
small  doses  of  a  killed  culture  can  produce  immunity  in  a  person  who 
is  constantly  swallowing,  both  on  an  empty  stomach  and  otherwise, 
large  doses  of  his  own  micro-organisms  in  a  fluid  of  his  ov^m  secretion. 


78  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

yet  I  must  admit  that  one  or  two  cases  have  come  under  my  own 
observation  in  which  it  appears  that  immunity  has  been  so  produced. 
In  such  instances,  therefore,  as  the  following,  (i)  when  the  subcutaneous 
administration  of  even  tiny  doses  produces  an  undesirable  reaction,  (2) 
when  the  patient  refuses  to  submit  to  puncture,  or  persistently  collapses 
or  faints  under  the  inoculation — and  I  have  met  with  several  such 
cases,  (3)  when  the  patient  is  going  out  of  reach  of  medical  men,  and 
desires  to  continue  treatment,  (4)  that  of  infants  or  of  very  young 
children;  the  oral  administration  of  the  vaccine  maybe  most  desirable. 
With  these  exceptions  inoculation  is  the  better  procedure,  for  no  doubt 
can  then  exist  of  the  actual  dose  of  vaccine  employed  to  stimulate  the 
tissues.  Hypodermic  injection  having  been  decided  on,  the  question 
of  site  remains  to  be  considered.  Intra-muscular  inoculation  has  been 
advocated  as  possessing  advantages  over  subcutaneous  ones  ;  it  is  held 
to  be  less  painful,  and  cause  less  tenderness,  while  the  bacteria  are 
more  readily  absorbed,  and  therefore  produce  more  speedy  immunising 
response ;  a  disadvantage  is  .the  greater  risk  of  puncturing  a  blood- 
vessel, and  of  introducing  the  inoculum  therein.  This,  however,  is  not 
a  very  real  danger,  for  the  endeavour  to  withdraw  the  piston  will  soon 
indicate  whether  the  needle-point  is  within  a  vein.  Subcutaneous 
inoculation  is- that  most  commonly  practised;  the  best  sites  are  where 
subcutaneous  tissue  is  lax,  and  no  pressure  by  clothes,  or  otherwise, 
v*'ill  be  exerted  upon  the  site.  For  these  reasons  the  tissues  of  the  arm 
or  leg  should  be  avoided,  whereas  the  following  localities  are  highl}^ 
suitable :  (i)  the  upper  buttock  2-3  in.  from  the  medium  line ;  (2)  the 
flank  or  abdomen  in  well-covered  individuals ;  (3)  ii-2  in.  below  the 
centre  of  the  clavicle. 

The  procedure  is  as  follows :  take  an  all-glass  syringe  with  sharp, 
clean  needle,  best  of  platinum-iridium,  in  default  of  this  of  steel.  Sterilise 
the  glass  parts  separately  by  boiling  in  distilled  water,  a  platinum- 
iridium  needle  by  boiling,  or  passage  through  a  flame,  a  steel  needle  by 
boiling  in  methylated  spirit,  and  put  the  parts  together  by  means  of 
sterile  forceps  ;  shake  up  the  bacterial  emulsion  thoroughly,  nick  the 
neck  of  the  containing  bulb  with  a  file  or  glass-knife  and  snap  it  off; 
invert  the  bulb  over  the  needle-point,  and  aspirate  the  contents  into  the 
syringe.  Sterilise  the  skin  of  the  patient  at  the  selected  spot  with 
iodine,  10  per  cent,  lysol,  or  alcohol  and  then  ether,  pick  up  a  good  fold 
of  tissue  firmly  between  left  thumb  and  forefinger,  boldly  plunge  the 
needle  into  the  tissues,  subcutaneous  or  muscular,  as  is  wished,  and 
slowly  introduce  the  inoculum  therein ;  withdraw  the  needle  quickly. 
These  precautions  amply  suffice  to  preclude  septic  infection,  and  ensure 
the  minimum  of  discomfort. 


CHAPTER    VI. 

IV  (I)  VACCINES  IN  THE  TREATMENT  OF  NASAL  AND 
POST-NASAL  CATARRH,  TRACHEITIS  AND  LARYN- 
GITIS, AND  INFECTIONS  OF  THE  ACCESSORY 
SPACES. 

In  the  treatment  of  ordinary  catarrhs  the  following  points  require 
consideration  : 

{a)  At  what  period  of  an  attack  to  begin  immunisation. 
{b)  At  what  time  of  day  to  perform  inoculation. 

(c)  The  initial  and  subsequent  dosages  and  intervals. 

[d)  General  treatment. 

(f)  Advantages  of  specific  treatment  and  results  to  be  expected. 

Let  us  consider  these  seriatim. 

(a)  The  period  of  an  attack  at  which  to  commence  imnninisation. — 
Formerly  I  used  to  consider  it  inadvisable  to  inoculate  during  the 
first  three  days  of  an  acute  attack  and  thought  it  wise  to  defer 
interference  until  the  inception  of  the  subacute  stage.  This  attitude 
was  brought  about  by  observing  the  effects  produced  by  the  dosages 
I  then  employed.  Now  I  know  that  the  occasionally  unpleasant 
sequelae  were  due  entirely  to  excessive  dosage,  and  am  sure  that 
the  earlier  we  begin  specific  treatment  the  better.  How  soon  this 
may  be  done  depends  on  several  factors,  such  as — (i)  the  stage  at 
which  we  are  consulted  ;  obviously  if  we  are  not  called  in  at  the  incep- 
tion we  cannot  inoculate  at  the  inception  ;  (2)  does  the  patient  insist 
upon  the  use  of  an  autogenous  vaccine,  or  will  he  content  himself  with 
a  stock  one  to  begin  with  ?  In  the  former  case  at  least  twenty-four 
hours  will  be  consumed  in  the  preparation  of  the  vaccine.  In  the 
latter  event  it  will  depend  partly  upon  the  accuracy  of  the  patient's 
description,  partly  upon  our  own  skill  in  making  therefrom  the  correct 
differential  diagnosis.  If  there  be  any  doubt  upon  this  point  a  combined 
vaccine  of  the  various  catarrhal  organisms,  or  at  all  events  of  such  of 
them  as  are  known  to  be  concerned  in  the  production  of  the  existing 
epidemic,  must  be  employed.     (3)   Is  the  patient  able  to  present  himself. 


8o  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

or  can  a  visit  be  paid  at  the  time  of  day  suited  for  the  inoculation,  and 
is  it  possible  for  him  subsequently  to  observe  the  necessary  precautions  ? 
(see  section  b).  If  these  conditions  cannot  be  fulfilled,  then  it  is  better 
to  wait  for  two  to  three  days  until  the  subacute  stage  has  been 
entered  on. 

(b)  At  what  time  of  day  to  perform  inoculation. — Acute  catarrhs  are 
an  infectious  disease,  fraught  with  possible  dangers  not  only  to  the 
patient  but  to  those  with  whom  he  comes  in  contact.  If  this  were 
adequately  realised  their  incidence  and  mortality  would  be  much 
reduced.  No  one  suffering  from  acute  catarrh  should  attend  a  public 
gathering  or  sneeze  into  the  air,  but  into  the  folds  of  a  handkerchief 
moistened  with  a  few  drops  of  formalin,  or  above  all  allow  anyone  to 
come  in  contact  with  him  to  whom  an  acute  catarrh  would  prove  of 
especial  danger,  such  as  the  very  young,  the  old  and  infirm,  those 
suffering  from  impairment  of  the  heart's  action,  or  some  other  respira- 
tory disease.  Per  contra,  bed  is  the  ideal  place,  in  a  well-ventilated 
but  warm  room,  attended  by  a  suitable  nurse,  who,  when  in  attendance, 
should  cover  the  mouth  and  nose  with  a  pad  of  lint  upon  which  a  drop 
or  two  of  formalin  has  been  sprinkled.  If  the  patient  can  follow  these 
instructions  inoculation  may  be  performed  at  any  time  of  day,  but  best 
at  night  between  7  and  10  p.m.,  as  then  the  least  interference  with  the 
night's  repose  is  brought  about. 

In  the  event  of  a  commencing  cold  there  is  no  particular  objection 
to  the  patient  making  call  upon  his  way  home  after  the  day's  work  is 
done.  By  immediately  going  home,  eating  a  light  dinner  and  retiring 
early  he  will  avoid  all  danger  of  exacerbation  of  the  attack.  A  similar 
procedure  is  suitable  in  the  case  of  chronic  colds,  but  none  the  less  it 
is  always  preferable  to  give  a  first  inoculation  when  the  patient  is  in 
bed.  Subsequent  doses  may  be  given  any  time  after  3  p.m.  provided 
the  patient  is  proceeding  home  and  will  follow  the  precautions  above 
■described ;  still,  the  later  in  the  day  the  better ;  personally  I  prefer 
between  5  and  7,  the  earlier  time  in  winter  and  the  later  in  summer. 

(c)  The  initial  doses  of  the  various  organisms  which  may  be  safely 
•employed  in  the  first  few  days  of  an  acute  catarrh  are  us  follows  : 
B.  septus,  50  millions;  M.  catarrhalis,  25  millions;  M.  para-tetragenus, 
25  millions  ;  pneumococcus,  25  millions  ;  B.  influenzcB,  50  millions;  B.  of 
Frie'dlander,  50  millions.  These  may  be  used  singly  or  in  any  combina- 
tion. The  effects  to  be  expected  from  such  an  administration  are  as 
follows  :  During  the  ensuing  twelve  to  eighteen  hours  there  may  be 
.a  slight  exacerbation  of  all  the  symptoms,  slight  headache  and  malaise, 
acceleration  of  pulse  by  ten  to  fifteen  beats,  and  rise  of  temperature  of 
i°-i"5°  F.  Any  one  or  more  of  these  constitute  a  reaction.  The  sub- 
sidence of  these  may  be  very  rapid,  and  within  twenty-four  hours  the 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  8  I 

improvement  in  the  patient's  symptoms  and  feeling  of  well-being  may 
be  quite  marked.  The  absence  of  any  reaction  or  of  improvement 
within  forty-eight  hours  is  indicative  of  the  immediate  advisability  of 
giving  a  double  dose  ;  failure  to  react  to  this  almost  certainly  points  to 
faulty  diagnosis  of  the  infecting  organisms,  and  fresh  smears  and 
cultures  should  at  once  be  made.  Should  the  patient,  on  the  contrary, 
react  in  any  of  the  above  ways,  re-inoculation  may  be  deferred  until 
retrogression  occurs — but  this  is  hardly  a  good  practice — or,  better,  be 
performed  upon  the  fourth  or  iifth  subsequent  evening.  The  indica- 
tions, then,  both  of  dosage  and  intervals  consist  in  the  clinical  signs  and 
S5'mptoms  and  in  the  production  of  a  mild  reaction.  The  inadvisability 
of  ever  increasing  dosage  so  long  as  adequate  responses  are  made 
should  be  ever  borne  in  mind,  while  the  possibility  of  an  incorrect 
diagnosis  of  the  infecting  organisms,  even  when  this  has  been  based 
upon  a  complete  bacteriological  examination,  is  always  suggested  by 
failure  to  respond  in  any  way  to  the  double  dosage  above  indicated. 
Failure  to  continue  or  maintain  improvement  may  be  due  either  to 
inadequate  stimulation,  or  to  increased  vitality  on  the  part  of  one  of 
the  infecting  agents  in  a  mixed  infection,  and  so  to  inadequate  dosage 
of  that  particular  vaccine,  or  to  a  fresh  infection  by  another  microbe  ; 
in  which  particular  direction  the  fault  may  lie  is  usually  elucidated  by 
a  bacteriological  examination. 

In  the  case  of  chronic  catarrhs  the  same  initial  dosage  as  for  acute 
infections  may  be  employed  ;  personally,  I  prefer  to  begin  with  the 
double  dosage,  as  reactions  are  both  milder  as  a  rule  and  more  difficult 
to  produce.  The  intervals  between  dosages  are  to  be  controlled  by  the 
reactions,  clinical  symptoms,  and  bacteriological  examinations.  The 
suitable  interval  I  find  to  vary  between  seven  and  ten  days.  As  before, 
it  is  inadvisable  ever  to  increase  the  dosage  so  long  as  either  (i)  a 
distinct  general  reaction  is  produced,  or  (2)  the  patient  continues  to 
improve  after  each  administration. 

A  chronic  catarrh  is  always  best  treated  with  the  autogenous 
vaccine,  and  the  following  points  should  always  be  clearly  borne  in 
mind  :  (i)  That  as  one  variety  of  a  micro-organism  is  eliminated 
another  may  come  to  the  front  ;  for  instance,  in  a  mixed  pneumo- 
coccus-B.  influenzcB  infection  it  is  no  uncommon  experience  to  find 
that  as  the  B.  injiueiizce  disappears  the  pneumococcus  comes  to  the 
front ;  the  patient,  so  far  from  making  marked  improvement,  ma}' 
even  appear  to  be  becoming  worse.  Careful  examination  of  smears 
and  cultures  will  reveal  this,  and  indicate  the  necessity  of  maintaining 
the  dosage  of  B.  injluenzce,  but  of  increasing  that  of  the  pneumococcus. 

(2)  That  a  fresh  acute  infection  of  some  other  prevailing  organism 
may    be    incurred,    and   mask    the    real    improvement    that    is    being 

6 


82 


thp:  bactkkial  i>iseases  of  respiration. 


produced  with  regard  to  the  chronic  infection.  Here,  again,  careful 
examination  of  smears  and  cultures  will  prevent  misconception,  and 
indicate  the  necessity  of  preparing  a  fresh  vaccine.  A  good  example  of 
a  case  like  this  is  related  by  Dr.  Roger  Smith  (Journal  of  Vaccine 
Therapy,  vol.  i,  No.  3,  p.  95). 

Briefly,  then,  increase  of  dosage  is  indicated  by  failure — 

(i)  To  obtain  a  slight  immediate  reaction ; 

(2)  To  secure  improvement  in  the  clinical  condition  after  any  dose, 
provided  that  the  possibility  of  (a)  increased  activity  on  the  part  of  one 
of  the  infecting  micro-organisms,  (6)  fresh  infection  by  another  bacterium, 
has  been  eliminated. 

Re-inoculation  is  indicated  by  slight  retrogression  or  failure  to 
continue  to  improve  on  the  part  of  the  patient  ;  experience  has  shown 
that  the  interval  between  inoculations  should  be  between  seven  and  ten 
days. 

(d)  General  treatment. — The  preliminaries  to  any  course  of  vaccine 
treatment  which  should  be  taken  have  been  already  fully  described;  in 
addition  general  treatment  on  more  or  less  stereotyped  lines  should 
also  not  be  neglected.  For  instance,  in  cases  of  acute  catarrh  the 
patient  should  be  confined  to  bed  in  a  warm,  well-ventilated  room, 
the  diet  restricted  in  regard  to  meat,  fish  being  an  appropriate  substi- 
tute ;  careful  attention  should  be  paid  to  the  bowels,  and  fluids 
limited  if  the  mucoid  discharge  be  unduly  copious.  It  is  most 
instructive  to  observe  the  effect,  say,  of  a  cup  of  tea  upon  the  nasal 
discharge  when  fluids  have  been  restricted  for  twenty-four  hours ; 
within  a  very  few  minutes  of  the  drink  the  secretion  of  mmcus  may  be 
increased  many-fold,  so  that  the  discharge  even  drips  away  from  the 
passages.  Handkerchiefs  should  be  sprinkled  with  two  or  three 
drops  of  pure  formalin,  and  a  silk  one  used  to  dry  the  nose  ;  by 
smearing  the  orifices  inside  and  out  with  a  little  resinol  or  boracic  oint- 
ment pamful  excoriations  may  be  obviated.  A  hot  foot-bath  of 
mustard  and  water  and  a  hot-water  bottle  to  the  feet  or  side  will 
increase  the  patient's  comfort ;  a  hot  drink  of  lemonade  or  whiske}- 
and  lemon,  followed  half  an  hour  later  by  a  dose  of  the  following 
prescription  by  Dr.  Burney  Yeo,  will  prom.ote  diaphoresis  and  the 
action  of  the  kidneys,  and  often  mitigate  or  shorten  the  attack  : 


.     Tct.  opii.  ...... 

.     vix. 

Vin.  ipecac.       ..... 

ITIX. 

Sp.  cether.  nit.  ..... 

5J- 

Liq.  ammon.  acet.     .          .          . 

5iij- 

Aq.  camph.  ad. 

^iss 

M.et.f.h. 

THE    BACTERIAL    DISEASES    OE    RESITRATION.  83 

An  additional  blanket  should  be  put  upon  the  bed,  and  in  the  event 
of  copious  sweating  being  produced  the  patient  should  be  urged  not  to 
withdraw  the  hands  from  beneath  the  covering,  nor  to  arise  in  the 
morning  before  cooling  off  by  degrees ;  the  above  prescription  may  be 
repeated  with  advantage  immediately  on  waking  in  the  morning. 

When  laryngitis  or  tracheitis  is  present  nothing  does  so  much  good 
as  the  application  of  a  cold  water  compress. 

Sprays  and  antiseptic  lozenges,  such  as  formamint,  conduce  to 
comfort  when  pharyngitis  or  tonsillitis  is  present,  but  in  the  value  of 
ammoniated  tincture  of  quinine  I  am  a  profound  disbeliever. 

Inhalations  of  steam  saturated  with  the  vapours  of  pure  eucalyptus 
or  cinnamon  oil  or  of  Friar's  balsam  sometimes  prove  of  service, 
but  rather  in  affections  of  the  lower  respiratory  tract  than  of  the 
upper. 


{e)  Advantages  accruing  from  Specific  Treatment. 

(i)  Acute  attacks  may  be  aborted  altogether  or  greatl}'  shortened 
in  duration.  In  the  great  majority  of  instances  the  patient,  if  seen  at 
the  inception  of  an  attack,  should  be  perfectly  able  to  resume  his 
duties  on  the  third  morning  after  the  first  inoculation  ;  when  confine- 
ment to  the  room  for  two  days  is  hardly  possible  it  is  perhaps  advisable 
to  begin  with  a  double  dosage  ;  the  reaction  will  be  greater,  but  so  will 
the  immunising  response,  and  this  should  be  well  established  after  an 
interval  of  eighteen  hours. 

(2)  The  risk  of  complications  is  greatly  minimised.  As  I  have  already 
said,  pneumococcal  infections  usually  begin  somewhere  about  the  larynx, 
influenzal  ones  probably  higher  up  the  tract.  Vaccine  treatment  will 
almost  certainly  prevent  extension  downwards,  and  I  think  I  am  under- 
stating the  truth  when  I  declare  my  belief  that  at  least  90  per  cent,  of 
the  cases  which  are  commonly  stated  to  have  died  of  pneumonia 
following  upon  influenza  could  have  been  saved  by  the  exhibition  of  a 
vaccine  at  the  commencement  of  the  attack  ;  even  in  the  later  stages, 
when  extension  to  the  chest  has  already  occurred,  more  than  50  per 
cent,  of  the  deaths  should  be  likewise  obviated.  As  I  wrote  some  years 
ago,  it  will  be  a  very  long  time  before  adequate  recognition  is  accorded 
to  this  fact ;  meanwhile  thousands  of  valuable  lives  will  be  needlessly 
sacrificed  at  every  epidemic. 

(3)  Chronic  sufferers  who  have  tried  almost  every  other  form  of 
treatment  will  be  either  cured  completely  or  afforded  a  considerable 
measure  of  relief. 

(4)  Subsequent  immunity,  more  or  less  complete,  may  be  secured 


84  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

against  future  acute  attacks ;  the  completeness  of  the  immunity  will 
depend — 

(a)  Upon  the  completeness  of  the  vaccine :  a  vaccine  containing, 
say,  pneumococcus,  B.  septus  and  M.  catarrhalis  can  hardly  be  expected 
to  afford  protection  against  the  B.  influenzcB. 

(b)  The  adequacy  of  the  treatment. 

(c)  The  choice  of  suitable  times  for  subjecting  the  patient  to  a  short 
course  of  treatment. 

For  the  production  of  immunity  against  acute  catarrhs  an  appro- 
priate vaccine  is  the  combined  vaccine  for  colds  of  the  Wimpole 
Institute,  w^hich  is  compounded  of  practically  all  the  catarrhal  organ- 
isms. It  should  be  employed  as  follows :  Inasmuch  as  the  average 
duration  of  complete  immunity  when  this  is  once  established  is  about 
six  months,  two  courses  of  treatment  should  be  given  in  each  year.  In 
England  the  end  of  September  or  the  beginning  of  October,  and  the  end 
of  January  to  the  beginning  of  March  usually  usher  in  an  epidemic  of 
acute  catarrhs.  The  patient  should,  therefore,  present  himself  for 
treatment  in  the  middle  of  September  and  the  middle  of  January.  A 
first  dose  of  50  millions  of  the  combined  vaccine  for  colds  should  be 
followed  at  ten-day  intervals  by  a  loo-million  and  a  250-million  dose. 
Thus,  by  the  end  of  the  first  week  in  October  and  the  first  week  of 
February  full  immunity  should  have  been  established,  and  it  may  be 
anticipated  with  a  certain  degree  of  confidence  that  any  prevaihng 
epidemic  may  be  escaped.  Against  the  Bacillus  influenza  it  is  a  difficult 
matter  to  secure  immunity  ;  probably  a  smaller  dosage  than  1000  or 
even  2000  million  organisms  will  not  prove  efficient  ;  personally  I  always 
warn  my  patient  that  immunity  against  this  organism  cannot  be 
assured. 

Post-nasal  catarrh  is,  as  a  rule,  a  chronic  infection  of  the 
naso-pharyngeal  space,  and  is  connected  clinically  and  astiologically 
rather  with  pyorrhoea  alveolaris  and  follicular  tonsillitis  than  with 
catarrhal  infections  of  the  other  portions  of  the  respiratory  tract ;  it  is 
a  very  important  cause  of  preventable  deafness.  I  have  in  the  past 
been  perhaps  somewhat  lax  in  differentiating  sufficiently  cases  of 
chronic  post-nasal  from  chronic  nasal  catarrh.  Accordingly  I  think 
that  the  figures  given  in  Table  VI  on  p.  46,  taken  from  C.  E.  West's 
paper  read  before  the  Otological  Section  of  the  Royal  Society  of  Medicine 
in  February,  191 2,  are  probably  more  reliable  than  my  own  given  in 
Table  III,  p.  44,  which  have  been  taken  from  cases  of  both  nasal  and 
post-nasal  catarrh. 

In  virtue  of  the  intimate  relationship  which  exists  between  this 
complaint  and  pyorrhoea  alveolaris  and  follicular  tonsillitis  the  absolute 
necessity  of  careful  search  for  these  latter  conditions  and  insistence 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  85 

upon  adequate  treatment  if  they  prove  to  be  present  prior  to  engaging 
upon  vaccine  treatment  of  the  post-nasal  catarrh  is  sufficiently  obvious. 
Only  rarely  is  this  condition  due  to  infection  by  a  single  organism, 
when  it  is,  the  bacillus  of  Friedlander  is  probably  the  one  concerned, 
mixed  infection  being  the  rule ;  streptococcus,  pneumococcus,  M. 
catarrhalis  and  Staphylococcus  aureus  may  be  present  in  any  combination. 
Autogenous  vaccines,  therefore,  are  much  more  likely  to  prove  efficacious 
than  any  stock  one,  the  dosages  to  be  employed  are  similar  to  those 
indicated  for  the  treatment  of  chronic  nasal  catarrh  ;  the  intervals  are 
also  similar,  and  the  progress  of  the  case  is  also  to  be  estimated  by 
clinical  symptoms  and  bacteriological  examinations. 

My  own  results  have  been  particularly  good  ;  in  the  cases  which  I 
have  treated  for  otological  specialists,  such  as  Dr.  Greville  Macdonald, 
Mr.  Herbert  Tilley  and  Mr.  Seccombe  Hett,  the  report  by  these  observers 
has  always  been  that  the  disappearance  of  the  catarrh  has  been  very 
striking.  Unfortunately  the  influence  upon  the  deafness  has  not  been 
correspondingly  good,  the  cause  being  probably  the  extreme  chronicity 
of  the  cases.  My  own  private  cases  have  been  equally  satisfactory  as 
regards  the  catarrh  symptoms. 

West's  conclusions  in  regard  to  the  efficacy  of  the  treatment  are 
wisely  guarded,  as  his  experiments  have  not  yet  reached  finality.  He, 
however,  states  that  "  Friedlander  infections  seem  to  do  well  and 
catarrhalis  quickly  disappears  under  vaccine  treatment.  Staphylococcus 
aureus  seems  to  be  a  favourable  case  for  vaccination,  and  the  strepto- 
cocci certainly  diminish  or  disappear  in  some  cases.  On  the  other  hand 
the  pneumococcus  has  so  far  defied  my  efforts,  and  has  appeared  to  be 
just  as  numerous  and  just  as  effective  in  maintaining  catarrhal  processes 
after  lengthy  courses  of  vaccine  as  before  them.  It  may  be  that  fuller 
investigation  will  show  a  more  successful  method  with  pneumococcal 
infections,  either  by  the  use  of  still  larger  doses  or  by  employing  a 
vaccine  from  a  specially  virulent  strain."  In  default  of  definite  infor- 
mation as  to  dosage  it  is  difficult  to  judge  how  far  this  surmise  maj^  be 
true  ;  probably  it  is  justified,  my  own  experience  being  that  ultimate 
dosages  of  500  or  even  1000  million  pneumococci  are  sometimes 
requisite.  As  regards  the  second  point  I  think  the  fault  may  possibly 
lie  in  the  method  of  preparation  of  the  vaccine.  As  I  have  already 
said,  sometimes  a  pneumococcal  vaccine  sterilised  by  heat  is  devoid  of 
immunising  power  while  one  sterilised  by  antiseptic  alone  secures  an 
immediate  response.  At  the  same  time  I  must  admit  that  I  also  have  at 
times  found  it  impossible  to  prepare  by  any  means  an  efficient  vaccine 
from  certain  strains  of  pneumococcus. 

The  effect  of  vaccine  treatment  upon  chronic  Etcstachian  catarrh 
has  been  very  striking  so   far  as  the  catarrh  itself  is   concerned,  but 


86  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

disappointing  as  regards  any  marked  improvement  of  the  actual 
hearing ;  inasmuch,  however,  as  all  my  cases  have  been  ones  of  very 
old  standing,  as  a  rule  of  about  twenty  years  or  more,  complicated 
perhaps  by  some  degree  of  oto-sclerosis,  and  had  been  already 
subjected  to  all  such  other  methods  of  treatment  as  the  skill  of  well- 
known  specialists  could  devise,  the  production  of  even  a  slight  degree 
of  improved  audition  should,  I  suppose^  be  considered  satisfactory ;  in 
perhaps  50  per  cent,  of  my  cases  this  has  been  obtained.  The  best 
effects  have,  however,  been  the  prevention  of  acute  outbursts  of  the 
Eustachian  catarrh  and  the  resultant  mamtenance  of  the  hearing  at  a 
more  steady  level. 

In  acute  otitis  media  vaccines  appear  sometimes  to  prove  of  very 
great  service  in  clearing  up  the  infection  ;  there  is,  however,  no  little 
difficulty  in  estimating  their  precise  effect ;  for  inasmuch  as  puncture 
or  incision  of  the  membrane  is  requisite  for  obtaining  cultures,  and 
this  procedure,  combined,  of  course,  with  such  other  measures  as 
experience  indicates,  frequently  of  itself  brings  about  a  speedy  cure, 
the  good  results  seen  after  exhibition  of  a  vaccine  cannot  with  any 
degree  of  certainty  be  allocated  in  any  particular  case  to  this  or  that 
form  of  treatment.  When,  however,  perforation  of  the  drum  has 
spontaneously"  occurred  and  the  infection  does  not  appear  to  yield  to 
the  more  stereotyped  methods  of  treatment,  the  effect  of  vaccine  treat- 
ment can  be  better  gauged.  One  case  in  which  double  otitis  media, 
consequent  upon  an  attack  of  scarlet  fever,  responded  with  striking 
rapidity  and  completeness  to  inoculations  of  the  autogenous  staphylo- 
coccal and  streptococcal  vaccines  I  have  already  recorded  (see  Lancet, 
September  nth,  1909,  p.  780).  The  membranes  healed  with  hardly 
any  trace  of  scarring  and  the  hearing  when  examined  six  months  later 
by  a  well-known  aurist  was  found  practically  normal. 

In  more  chronic  cases  it  is,  of  course,  easier  to  arrive  at  a  just 
appreciation  of  the  value  of  vaccine  treatment.  Good  results  have 
been  obtained  in  infections  due  to  the  B.  proteus,  B.  pyocyaneus, 
B.  coli,  streptococcus,  pneumococcus,  staphylococcus ;  inasmuch  as 
there  is  always  a  tendency  for  the  infection  to  change  in  character, 
occasional  bacteriological  examinations  of  the  secretion  are  very 
essential. 

The  case  for  vaccine  therapy  in  otitis  media,  acute  or  chronic,  may 
be  fairly  summarised  as  follows  :  It  can  do  no  harm,  while  it  will  almost 
certainly  prove  a  valuable  adjunct  to  other  forms  of  treatment  in 
hastening  the  healing  process,  limiting  the  extent  of  damage  and  con- 
sequent scarring  of  the  membrane  and  iixation  of  the  ossicles  and 
in  diminishing  the  risk  of  intra-cranial  complications. 

In  acute  infections  the  following  initial  dosages  may  be  employed  : 


THE    BACTERIAL    DISEASES    OE    RESPIRATION.  87 

Streptococcus,  10  to  25  millions  ;  pneumococcus,  10  to  25  millions  ; 
staphylococcus,  50  millions;  B.  pvoteus,  50  millions;  B.  pyocyaneiis, 
50  millions ;  B.  infliienzce,  50  to  100  millions  ;  M.  catarrhalis,  25  mil- 
lions. Higher  initial  dosages  than  these  are  not  advisable  unless  very 
free  drainage  be  maintained,  for  increased  discharge  and  augmented 
pain  usually  ensue  for  twelve  to  eighteen  hours.  Undue  haste  in 
increasing  subsequent  dosages  is  also  to  be  deprecated,  for  these  cases 
appear  to  make  good  progress  upon  small  doses.  The  usual  interval 
is  about  five  days  or  rather  longer. 

In  chronic  cases  trial  may  be  made  with  like  amounts,  but  in 
default  of  progress  augmentations  may  be  made  rapidly  with  little 
hesitation.  I  have  m3^self  used  500-million  doses  of  B.  pyocyaneus 
and  looo-million  doses  of  B.  pvoteus  with  very  good  result  and  no  ill- 
effects. 

In  infections  of  the  antrum  and  accessory  spaces,  we  are  confronted 
by  no  little  difficulty  in  arriving  at  a  just  appreciation  of  the  scope 
and  value  of  vaccine  treatment.  As  to  the  frequency  with  which 
involvement  of  one  or  more  of  the  accessory  sinuses  occurs  during 
attacks  of  acute  rhinitis  statistics  are  wholly  lacking.  Personally 
I  think  that  it  does  occur  in  at  least  80  per  cent,  of  all  cases, 
and  that  it  is  especially  frequent  in  acute  catarrhs  due  to  the 
B.  influenza;,  M.  catarrhalis  and  pneumococcus.  If  this  be  so  spon- 
taneous cure  must  be  very  frequent.  The  rapidity  with  which  an 
antrum  full  of  pus  can  clear  up  is  very  striking.  I  have  observed  a 
complete  shadow  as  seen  by  transillumination  entirely  disappear  within 
thirty-six  hours  and  not  recur.  The  ease  with  which  this  can  happen 
must  obviously  largely  depend  upon  the  position  of  the  opening  with 
regard  to  the  floor  of  the  cavity.  If  this  be  near  the  floor  evacuation 
is  easy;  the  higher  up  it  is  the  greater  the  obstruction  to  natural 
drainage.  The  poorness  of  the  blood  supply  and  the  scanty  amount  of 
tissue  covering  the  bony  walls  make  it  difficult  to  understand  how  the 
copious  exudate  is  formed  and  the  mechanism  whereby  absorption 
occurs  of  the  residue  which  fails  to  drain  away.  The  fact  remains  that 
several  drachms  of  pus  may  be  secreted  daily  and  that  spontaneous 
evacuation  and  absorption  may  occur  with  extreme  rapidity. 

It  is  therefore  with  considerable  hesitation  that  an  expensive  course 
of  vaccine  treatment  should  be  suggested  to  any  case  of  acute  infection 
of  the  antrum  until  opportunity  for  spontaneous  cure  has  been  afforded 
and  aided  by  attention  to  intra-nasal  abnormalities,  the  institution  of 
facilities  for  proper  drainage  and  the  application  of  lavage  and  other 
usual  remedial  measures. 

Here  I  would  like  to  say  that  if  artificial  drainage  has  to  be 
established,  and   the   possibility  of  future  vaccine  treatment    has   to 


88  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

be  considered,  then  an  intra-nasal  operation  will  be  a  better  procedure 
than  puncture  through  a  tooth-socket,  for  this  latter  affords  unlimited 
opportunity  for  the  continual  ingress  of  contaminating  organisms  from 
the  mouth,  organisms  which  may  prove  especially  refractory  to  vaccine 
treatment.  As  soon,  however,  as  an  acute  infection  shows  a  tendency 
to  assume  a  chronic  state  resort  should  be  m.ade  to  vaccine  therapy  for 
the  following  reasons :  (i)  Extension  to  neighbouring  cavities  may  be 
obviated ;  (2)  truly  chronic  infections  prove  decidedly  refractory  to 
specific  treatment.  In  by  far  the  greater  proportion  of  the  thirty  cases 
which  I  have  seen  during  the  past  three  years  operative  measures  had 
been  taken,  and  lavage  persisted  in  for  several  j'ears.  In  none  of  these 
have  I  succeeded,  even  after  two  years'  treatment,  in  producing  such 
complete  cure  that  vaccine  treatment  could  be  altogether  discontinued. 
What  I  have  achieved  has  been  as  follows  :  (i)  Great  diminution  of  the 
secretion,  perhaps  to  such  a  degree  that  the  performance  of  lavage 
once  every  two  or  three  days  by  the  patient  himself  has  sufficed  to 
maintain  a  practically  complete  absence  of  pus  formation ;  (2)  total 
disappearance  of  exacerbations  and  of  recurrent  attacks  of  acute  nasal 
catarrh  ;  (3)  considerable  improvement  in  the  general  health.  The 
best  results  I  have  obtained  have  been  in  two  very  chronic  cases,  one 
of  infection  by  the  bacillus  of  Friedlander,  the  other  by  the  B.  coli. 
In  each  of  these  operative  interference  was  refused,  and  could  not  be 
insisted  on,  yet  the  final  result  was  almost  complete  cure ;  a  short 
course  of  vaccine  treatment,  has,  however,  had  to  be  continued  at  four- 
to  six-monthly  intervals. 

If  any  measure  of  success  is  to  be  achieved  in  these  very  chronic  cases 
it  must  be  remembered  (i)  that  very  high  ultimate  dosages  indeed  may 
be  requisite,  such  as  2000,  or  even  5000  million  B.  influenzce,  1000- 
2000  miillion  pneumococcus,  1000  million  streptococcus  or  M.  catarrhalis, 
1000-2000  B.  of  Friedlander,  B.  coli  or  B.  proteus,  2000-4000 
million  staphylococcus.  The  blood  supply,  especially  to  the  antrum, 
frontal  and  sphenoidal  sinuses  is  small,  hence  the  amount  of  immune 
bodies  carried  there  is  small  in  any  given  blood  volume;  as  there  is 
difficulty  in  increasing  the  latter  it  is  necessary  greatly  to  augment  the 
former. 

(2)  That  treatment  may  have  to  be  prolonged,  and  should  be  re- 
continued  after  intervals,  say,  of  every  six  months. 

(3)  That  in  cases  of  multiple  sinusitis  the  bacterial  flora  of  the 
several  cavities  may  differ,  and  that  great  care  is  requisite  in  making  a 
correct  bacteriological  diagnosis,  and  in  checking  the  progress  of  the 
immunisation. 

(4)  That  re-infection  or  fresh  infection  by  other  bacteria  may  at  any 
time    occur;  inasmuch   as  the  most  likely  new  invaders  are  the  other 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  89 

catarrhal  organisms  a  wise  procedure  is  to  anticipate  the  possibility,  as 
far  as  possible,  by  the  administration,  at  six-monthl}-  intervals,  of  three 
progressive  doses  of  the  combined  vaccine  for  colds  of  the  Wimpole 
Institute. 

(5)  That  when  large  dosages  are  being  employed  the  intervals 
must  not  be  unduly  short  ;  ten  days  or  slightly  longer  usually  proves 
a  satisfactory  one. 

(6)  That  if  progress  is  interrupted  fresh  infection  is  a  most  likely 
cause,  and  is  to  be  determined  by  careful  reinvestigation  of  the 
bacterial  flora. 


CHAPTER   VII. 
VACCINES    IN    BRONCHITIS   AND    ASTHMA. 

(a)  Bronchitis. — This  condition  is  one  pre-eminently  suited  for 
vaccine  treatment.  The  diagnosis  of  the  offending  organisms  presents 
few  difficulties  ;  a  suitable  vaccine  and  therefore  the  production  of  the 
necessary  immune  bodies  can  be  obtained  with  reasonable  certainty  ; 
the  copious  blood-supply  ensures  the  carriage  of  these  latter  to  the 
focus  of  disease,  and,  as  I  shall  show,  there  are  definite  methods  of 
estimating  the  progress  made  and  so  of  controlling  intervals  and 
dosage.  Reference  to  Table  X,  p.  53,  will  show  that  five  organisms, 
viz.  the  B.  iilflnenza,  pneumococcus,  streptococcus,  M.  catarrhalis 
and  M.  paratetragenus  are  chiefly  concerned  in  the  production  of  this 
condition;  they  may  occur  singly — a  rare  event — or  in  any  of  the 
varying  combinations ;  usually  two  or  three  varieties  occur  together. 
While  in  many  cases  involvement  of  the  bronchi  and  bronchioles  is 
sequent  to  acute  catarrh  of  the  upper  respiratory  tract,  yet  in  certain 
cases,  especially  in  the  old  and  infirm,  and  in  those  specially  prone  to 
bronchial  infections,  the  involvement  of  the  lower  passages  would 
appear  to  be  the  primary  one ;  in  these  instances  the  infection  is  the 
more  likely  to  be  a  simple  one.  Streptococci  are  of  considerably  more 
importance  in  catarrhs  of  the  lower  respiratory  tract  than  of  the  upper, 
and  may  belong  either  to  the  so-called  "  salivariiis"  type,  or  to  the 
varieties  depicted  in  figs.  7  and  10,  Plate  III;  these  latter  when  present 
would  appear  to  be  of  special  importance. 

It  is  fairly  obvious  that  autogenous  vaccines  are  more  likely  to  be 
efficacious  in  the  treatment  of  this  complaint  than  are  stock  ones,  and 
it  is  especially  important  to  bear  in  mind  that  variation  in  the  flora  is 
very  liable  to  occur  during  the  progress  of  immunisation,  and  that  a 
blend  of  vaccine  admirably  adapted  for  treatment  at  the  beginning  may 
be  totally  unsuited  to  the  later  stages;  if  this  be  carefully  remembered, 
much  disappointment,  both  to  immuniser  and  patient,  will  be  avoided. 
In  early  stages  of  the  acute  bronchitic  attack  bacteria  may  be  few,  the 
sputum  being  composed  chiefly  of  hyalin  mucus  containing  bronchial 


THE    BACTERIAL    DISEASES    OE    RESPIRATION.  9 1 

cells  in  a  state  of  rapid  degeneration  ;  at  the  height  of  the  attack 
mononuclear  pulmonary  cells  make  their  appearance,  indicative  of 
-extension  of  the  process  to  the  terminal  bronchioles  and  even  the  alveoli ; 
during  subsidence  the  hyaline  mucus  becomes  replaced  by  large  mucous 
networks,  containing  within  the  meshes  many  bacteria  and  polymorpho- 
nuclear leucocytes.  The  examination  of  smears  suitably  stained  with 
Unna's  polychrome  blue  or  in  default  of  this  with  Leishman's  stain 
thus  affords  a  fairly  reliable  guide  as  to  the  stage  and  progress  of 
the  infection.  The  daily  measurement  of  the  sputum  and  its  naked-eye 
appearance,  the  pulse  and  temperature  also  prove  of  service  in  esti- 
mating the  patient's  progress.  The  most  accurate  method  of  controlling 
intervals  and  dosage,  one,  moreover,  applicable  to  all  infections  of  the 
lower  respiratory  tract,  is  that  based  upon  careful  stethoscopic  observa- 
tion. The  procedure  depends  upon  the  following  facts:  (i)  that  any 
dose  of  vaccine  which  does  not  produce  a  definite  reaction  at  the  focus 
of  disease  is  either  inadequate  or  not  compounded  of  the  appropriate 
immunising  agents. 

(2)  That  such  a  dose  as  causes  definite  improvement  in  the  clinical 
signs  within  twelve  hours  is  affording  but  a  minimal  stimulus,  and  may 
probably  be  increased  with  some  advantage. 

(3)  That  such  a  dose  as  causes  definite  extension  of  the  signs 
within  twelve  to  eighteen  hours,  the  appearance  of  signs  where  none 
previously  existed,  or  an  increase  in  their  volume  or  moistness  is 
indicative  of  correct  dosage  provided  that  rapid  improvement  in  each 
of  these  particulars  ensues  within  the  next  few  hours. 

The  patient  having  been  placed  under  the  most  favourable  con- 
ditions, attention  having  been  paid  to  such  general  forms  of  treatment 
as  experience  indicates,  and  the  vaccine  having  been  prepared, 
systematic  stethoscopic  examination  of  the  chest  is  then  performed, 
and  the  clinical  signs  carefully  noted  upon  a  suitable  chart ;  the 
chest  charts  usually  employed  are  not  well  adapted  for  the  purpose, 
the  outlines  of  the  ribs  occupying  and  obscuring  too  much  of  the  space  ; 
a  much  better  form  has  been  prepared  for  me  by  H.  K.  Lewis,  and  may 
be  seen  in  Charts  V-XI  ;  ample  room  is  afforded  for  the  insertion  of 
such  signs  as  we  may  employ,  those  indicated  on  the  margin  being 
■convenient,  and  affording  at  a  glance  such  information  as  ma}'  be 
desired. 

The  selected  dose  of  vaccine  is  then  administered  and  fresh 
•observations  taken  at  the  end  of  twelve  and  twenty-four  hours  and 
daily  thereafter.  Assuming  that  a  definite  reaction  has  been  first 
produced,  steady  improvement  in  the  condition  is  indication  of  with- 
holding any  fresh  inoculation,  at  all  events  for  seven  or  eight  days, 
unless   retrogression    occurs,   especially  if   this  be  accentuated   upon 


92  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

observation  twenty-four  hours  later,  when  the  necessity  of  reinoculation 
is  thereby  indicated.  Increase  of  dosage  is  necessary  when  improve- 
ment is  maintained  for  only  three  or  four  days,  or  in  default  of  adequate 
response. 

Front   of  Chest  Back  of  Cheat 


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Chart  V. — Before  first  inoculation.     Sputum  =  6  oz.  per  day, 


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Chart  VI. — Twelve  hours  after  first  inoculation.     Sputum  =  lo  oz.  per  day. 


Gharts  V-XI  will  serve  to  elucidate  my  meaning,  and  show  admirably 
the  progress  made  by  a  certain  severe  case  of  acute  recurrent  bronchitis 
in  an  aged  and  not  very  hopeful  case. 

The  patient  had  been  affected  for  at  least  ten  years  by  chronic  bron- 
chitis following  upon  an  attack  of  apparently  true  influenza — three  or 
four  times  during  each   of  the  last  three  j'ears  there  had  been  acute 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


93 


exacerbations ;  the  attack  for  which  I  was  consulted  had  lasted  about 
a  fortnight,  respiration  was  very  much  embarrassed,  little  relief  was 
afforded  by  the  various  stock  remedies,  and  sleep  was  very  difficult  to 
procure.     When  I  saw  him  the  patient  looked  very  ill  indeed,  but  two 


Front   of  Chest 


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Chart  VII. — Twentv-fours  hours  after  first  inoculation.     Sputum  =  6  oz.  per  day. 


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Chart  VIII. — Seventy-two  hours  after  first  inoculation.     Sputum  =  2  oz.  per  day. 

good  features  were — (i)  the  pulse  was  regular  and  of  good  volume ;  (2) 
the  tissues  were  firm  and  apparently  healthy  despite  the  ill  look  of  his 
face.  A  bacteriological  examination  showed  that  the  sputum  was 
swarming  with  B.  influenzcs,  and  contained  also  many  pneumococci  and 
M.  catarrhalis.  An  autogenous  vaccine  was  prepared  of  each  of  these, 
and  treatment  begun  with  a  dose  of  50  million  B.  influenzcB  and  25 


94 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


million  each  pneumococcus  and  M.  catarrhalis.  As  will  be  seen  from 
the  charts  a  marked  local  reaction  was  produced  within  twelve  hours, 
the  physical  signs  being  increased  considerably,  as  was  also  the  amount 
of  sputum  ;  of  constitutional  symptoms  there  were  none  beyond  slight 


Front    of  Chest 


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Chart  IX. — Six  days  after  first  inoculation.     Second  inoculation.     Sputum  =  3  oz.  per  day. 


Front 
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Chart  X. — Twelve  hours  after  second  inoculation.     Sputum  =  4  oz.  per  day. 

increase  of  pulse-rate.  At  the  end  of  twenty-four  hours  improvement 
began  to  set  in,  and  the  patient  passed  the  best  night  for  a  fortnight  ; 
the  improvement  continued  markedly  during  the  next  three  days,  then 
there  was  a  slight  relapse.  Accordingly  on  the  completion  of  the  sixth 
day  the  initial  dose  was  repeated,  again  with  such  highly  beneiicial  results 
that  at  the  end  of  the  eighth  day  after  beginning  the  vaccine  treatment 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


'5 


the  patient  was  sleeping  well,  only  being  awakened  by  one  or  two  slight 
fits  of  coughing,  was  able  to  recline  in  comfort,  was  eating  well,  and 
expectorated  only  i  oz.  of  sputum  in  the  twenty-four  hours.  Con- 
valescence was  uninterrupted,  and  the  patient,  instead  of  leaving  for 
Madeira,  as  had  been  intended,  was  able  to  winter  on  the  south  coast 
of  England.  Inoculations  were  continued  at  intervals  of  six  to  eight 
days,  and  about  two  months  after  the  beginning  of  treatment  exami- 
nation of  the  sputum  shov,^ed  a  reduction  in  the  organisms  by  many 
hundredfold ;  the  same  varieties,  however,  were  still  present,  and 
expectoration  persisted  to  the  extent  of  2-3  drachms  per  day.  At  this 
time  a  dosage  of  250  million  B.  influenzce  and  100  million  M.  catarrhalis 
and  pneumococcus  was  being  employed.     I  therefore  advised  the  use 


Front    of  Chest 


Back  of  Chest 


POST^TUSSK 
RALE 


PRU  -TUSSIC 
DKY-KALe 

00 

000  = 
o 
PP/t  -TUSSIC 

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RHOHChUS 


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Chart  XI. — Forty-eight  hours  after  second  inoculation.     Sputum  =  ^  oz.  per  day. 

of  double  this  dosage  at  intervals  of  eight  days.  At  the  end  of  another 
two  months  further  slight  reduction  in  the  amount  of  sputum  had  been 
attained,  and  examination  showed  that  the  B.  infliienzcB  had  almost  if 
not  entirely  disappeared  (none  at  all  could  be  cultured);  the  pneu- 
mococci  had  also  gone,  but  the  M.  catarrJialis  had  somewhat  increased 
in  actual  numbers.  A  fresh  vaccine  was  therefore  prepared,  and 
treatment  continued  with  dosages  of  250  millions  at  eight-day  intervals. 
The  patient  is  now  practically  well,  merely  expectorating  one  or  two 
nummular  masses  of  sputum  on  waking ;  these  contain  nothing 
but  a  few  M.  catarrhalis.  With  this  condition  the  patient  is 
well  satisfied,  and  it  merely  remains  to  forestall  fresh  infections  by 
the  use  of  two  or  three  immunising  doses  about  every  four  months, 
suitable  administrations  being  the  following  sequence  at  eight-  to  ten-day 
intervals:   (i)  B.  inflnenzce  100  millions,  pneumococcus  50  millions,  M. 


96  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

catarrhalis  loo  millions  ;  (2)  B.  influenzce  250  millions,  pneumococcus 
100  millions,  M.  catarrhalis  250  millions ;  (3)  B.  influenzce  500  millions, 
pneumococcus  250  millions,  M.  catarrhalis  500  millions.  Should, 
despite  this,  a  fresh  attack  occur,  the  first  essential  will  be  a  re-exami- 
nation of  the  sputum  in  case  infection  has  been  set  up  by  some  other 
organism.  If,  however,  one  of  the  old  ones  shall  have  again  come  to 
the  front,  the  determination  of  suitable  dosage  will  depend  upon  the 
interval  that  has  elapsed  since  the  last  immunising  dose  ;  if  this  has 
been  recent,  say  within  a  month,  then  treatment  will  be  begun  with  the 
second  of  the  above  three  dosages;  if  on  the  contrary  it  is  near  the  end 
of  the  four  months'  interval,  then  with  the  first  of  these;  but  rapid 
advance  in  dosage  will  probably  prove  advisable  (this,  however,  will 
be  determined  as  before  by  stethoscopic  and  other  observations). 

I  could  relate  the  histories  of  many  cases  similar  to  the  above,  but 
this  would  prove  of  httle  advantage;  for  inasmuch  as  the  careful  clini- 
cian will  find  no  difficulty  whatever  in  understanding  the  rationale  of 
the  above  procedure,  and  so  of  conducting  such  a  case  for  himself,  it 
only  remains  for  him  to  remember  that  the  other  essentials  to  a  suc- 
cessful issue  are — 

(i)  Accuracy  in  diagnosis  of  the  infecting  organism  or  organisms. 

(2)  Careful  preparation  of  the  appropriate  vaccine. 

(3)  Repeated  checking  of  the  progress  of  immunisation  by  means  of 
bacteriological  examinations,  which  will  at  once  indicate  whether 
change  of  vaccine  is  necessary. 

(4)  No  undue  haste  in  discontinuing  treatment  ;  for  so  long  as  the 
pneumococcus  or  B.  inflnenzcB  lurks  in  the  lung,  in  no  matter  how  scanty 
numbers,  it  is  always  a  source  of  continual  and  considerable  potential 
danger. 

(5)  The  application  of  all  other  such  adjuvants  as  clinical  experience 
has  proved  of  value. 

Old  age  and  a  desperate  condition  of  the  patient  are  no  contra- 
indications to  the  application  of  vaccine  treatment,  but  quite  the 
contrary  ;  they  merely  indicate  extra  care  in  the  choice  of  suitable 
dosages,  which  should  err  rather  on  the  side  of  under-dosage  than  on 
that  of  over-dosage ;  the  clinical  examination  of  the  chest  will  afford 
unerring  indication  as  to  whether  immunising  responses  are  being  made 
or  not ;  in  the  latter  event  dosages  must  be  pushed  and  intervals 
between  them  shortened,  to  three,  or  even  two  days  if  necessary,  until 
an  immunising  response  is  obtained  ;  when  this  has  been  achieved 
subsequent  increases  should  be  made  with  care  and  discretion,  and 
intervals  lengthened  if  so  indicated  by  the  clinical  observations. 

In  conclusion,  I  would  merely  add  that  I  have  never  seen  the  case 
which  did  not  benefit  immediately  and  markedly  from  the  administration 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  97 

of  the  suitable  vaccine  in  suitable  dosages  at  suitable  intervals,  and 
that  I  do  not  believe  such  a  case  exists ;  in  no  other  bacterial  infection 
of  any  part  of  the  body  are  such  gratifjnng  and  striking  results  to  be 
secured  ;  even  capillary  bronchitis  I  do  not  regard  as  beyond  the  reach 
of  this  form  of  treatment. 

(b)  Asthma. — When  we  consider  the  case  of  asthma  we  find 
that  we  are  dealing  with  an  affection  of  quite  a  different  kind. 
Bronchitis  is  a  bacterial  disease  and  nothing  else  ;  whereas,  were 
the  results  of  vaccine  treatment  in  asthmatic  conditions  not 
available,  it  would  be  impossible  to  assert  with  an}-  confidence 
that  asthma  is  ever  due  to  a  bacterial  infection.  The  fact, 
moreover,  that  vaccine  treatment  does  in  a  certain  percentage  of 
cases  prevent  the  onset  of  dyspnoeic  attacks — and  this  it  most  cer- 
tainly does — fails  to  establish  it  as  a  fact  that  the  bacteria  are  the 
true  cause  of  the  asthma ;  it  may  only  mean — and  this  I  believe  to 
be  the  case — that  a  bacterial  irritant  may  suffice  to  set  a  delicately 
poised  already  existent  mechanism  in  action — the  clock  may  be  wound 
up,  it  only  requires  a  touch  of  the  pendulum  to  set  the  works  in 
motion  ;  this,  in  certain  instances,  bacteria  or  their  toxins  suffice  to  do. 
It  thus  follows  in  some  cases,  where  due  attention  has  been  paid  (a)  to 
the  true  setiological  factor  of  the  asthmatic  spasm.  (6)  to  other  accessory 
factors,  such  as  diet,  condition  of  the  bowels,  place  of  residence,  etc., 
and  where  these  procedures  have  not  sufficed  to  cure  the  patient,  that 
benefit  will  accrue  from  therapeutic  immunisation.  That  this  would 
be  the  more  likely  to  occur  in  cases  where  bronchitic  symptoms  are 
marked,  expectoration  copious,  and  the  bacterial  flora  profuse,  might 
be  anticipated,  but  within  my  experience  this  is  not  necessarily^  so;  the 
best  results  are  oft  obtained  in  cases  characterised  by  the  scanty,  viscid, 
stringy  mucus  of  true  asthma,  containing,  relativel}^  to  a  bronchitic 
sputum^  but  few  bacteria  in  but  few  varieties. 

Although  I  fear  to  become  tedious  by  undue  repetitions,  here  more 
than  in  any  other  disease  with  which  bacteria  are  associated  is  it 
essential  to  ensure  that  proper  treatment  be  first  directed  to  all 
abnormalities,  errors  of  respiration  and  of  diet.  When  this  has  been 
done  and  the  usual  methods  for  securing  cure  or  alleviation  have  failed, 
resort  may  then  be  made  to  vaccine  treatment,  and  some  hope  of 
amelioration,  if  nothing  more,  may  be  offered  to  the  patient. 

Reference  to  Table  XI,  p.  54,  will  show  that  the  organisms  most 
commonly  found  in  the  sputum  of  asthma  are  the  streptococcus, 
M.  catarrhalis  and  pneumococcus. 

The  streptococcus,  which  may  be  brevis,  longiis,  or  maximus  in  type,  is 
present  in  no  less  than  96  per  cent,  of  all  cases,  and  within  my  experi- 
ence in  100  per  cent,  of  those  in  which  bronchitis  symptoms  are  in  abey- 

7 


98  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

ance ;  the  M.  catarrhalis,  on  the  other  hand,  is  the  more  common  in 
those  cases  in  which  bronchitis  is  a  marked  feature ;  this  also  holds  true 
for  the  B.  influenzce,  M.  paratetragenus  and  pneumococcus.  As  I  have 
already  said,  considerable  complexity  in  the  bacteriological  findings  is 
uncommon  ;  binorganismal  infection,  and  especially  by  a  streptococcus 
and  the  M.  catarrhalis,  is  that  most  frequently  found. 

The  nature  of  the  infection  is  not  without  bearing  upon  the  pro- 
gnosis of  the  vaccine  treatment;  if  the  Streptococcus  longus  or  maxiimts 
be  present,  amelioration  of  the  asthmatic  condition  under  judicious 
treatment  is  a  practical  certainty ;  if  the  M.  catarrhalis  predominates 
bronchitic  catarrh  is  sure  to  be  marked,  and  it  is  no  uncommon  result 
to  find  that  as  the  amount  of  the  bronchial  secretion  is  reduced,  the 
difficulty  in  expulsion  of  the  more  tenacious  and  more  truly  asthmatic 
sputum  becomes  increasingly  greater  and  the  tendency  to  spasms  more 
pronounced;  this  sometimes  indicates  that  streptococci  have  come  more 
to  the  front,  and  that  a  change  of  vaccine  is  probably  advisable,  but 
even  if  this  be  done  it  by  no  means  follows  that  a  favourable  result  will 
be  achieved,  and  personally  I  regard  the  steering  of  a  case  of  asthma  to 
the  desired  haven  as  difficult  a  manoeuvre  as  it  is  easy  in  a  case  of 
bronchitis. 

There  are  other  factors,  too,  which  prove  most  difficult  to  control. 
A  case  of  streptococcal  asthma  may  be  making  all  the  progress  one 
could  desire,  when  unhappily  a  fresh  bronchial  infection  by  the  pneumo- 
coccus or  more  especially  the  B.  influenzce  suddenly  occurs.  Not  only 
may  this  prove  difficult  to  eradicate,  but  the  unfortunate  result  is  also 
brought  about  of  a  resultant  unstabilising  of  the  already  none  too  stable 
centre  of  control  for  the  blood-supply  to  the  lung.  Dr.  Alexander 
Francis  tells  me  that  he  has  frequently  noticed  this  effect  produced  by 
infection  by  the  B.  influenzce  in  cases  wherein  he  has  stabilised  the 
vaso-motor  centre  by  means  of  cauterisation  of  the  nasal  mucosa, 
and  that  he,  too,  has  found  it  an  influence  peculiarly  difficult  to 
overcome. 

Lest,  however,  it  be  thought  that  the  vaccine  therapy  of  asthma  is 
so  fraught  with  difficulty  and  disappointment  as  to  be  nothing  worth, 
let  me  here  remark  that  in  a  certain  percentage  of  cases  the  results 
have  been  so  good  that  the  patients  utterly  refuse  to  discontinue  the 
occasional  use  of  their  vaccines,  but  every  six  months  or  so  go  through 
a  short  course  of  immunisation. 

The  initial  dose  of  the  various  vaccines  which  I  usually  employ  are 
as  follows :  B.  influenzce  loo  millions,  M.  catarrhalis,  M.  paratetragenus, 
and  pneumococcus  50  millions,  streptococcus  25  millions,  and  whether 
the  vaccine  is  likely  to  prove  of  service  or  not  will  be  almost  certainly 
determined  by  the  response  to  this  dose  or  to  one  of  double  magnitude. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  99 

During  the  night  of  the  inoculation  the  patient  will  be  awakened  by  an 
asthmatic  attack,  whether  he  be  usually  subject  to  one  or  not ;  in  the 
former  case  the  attack  may  be  a  bad  one  and  necessitate  control  either 
by  the  subcutaneous  injection  of  2-3  minims  of  adrenalin  solution 
I  in  1000,  or  by  whatever  means  is  usually  found  to  prove  efficacious  ; 
in  the  latter  case  the  attack  will  be  a  mild  one  and  pass  off  within  an 
hour  or  two.  If  the  patient  be  likely  to  benefit  by  the  treatment  and  such 
a  reaction  be  obtained,  during  the  ensuing  five  or  six  days  there  should 
be  increased  immunity  from  attacks  both  in  number  and  severity ; 
tendency  to  relapse  is  the  sign  for  re-inoculation;  failure  to  respond 
by  the  production  of  a  slight  attack  the  sign  for  increased  dosage. 
Occasionally,  it  is  true,  the  patient  does  not  react  to  the  dosage 
emplo3^ed  by  the  production  of  an  attack  within  twelve  hours,  but  by  a 
decided  lessening  in  the  number  and  severity  of  attacks;  this  indica- 
tion of  resulting  immunity  is  one  to  which  the  patient  will  take  no 
exception. 

My  observations  upon  the  vaccine  treatment  of  asthma  have  by  no 
means  yet  reached  finality,  and  it  is  therefore  impossible  to  be  very 
dogmatic  upon  any  point,  whether  of  bacteriology,  course  of  treatment 
or  results  ;  a  short  history  of  two  cases  will  serve,  perhaps,  to  illustrate 
some  few  points  which  I  have  endeavoured,  perhaps,  with  ill-success 
to  make  clear. 

Case  i. — Mrs.  A — ,  aged  23  years,  had  suffered  from  severe  asthma 
since  operation  for  adenoids  and  enlarged  turbinate  bones  two  years 
ago ;  paroxysms  very  severe,  lasting  several  hours,  and  for  the  past 
few  months  of  daily  occurrence.  As  she  was  perfectly  clear  in  her  own 
mind  that  the  asthma  was  due  to  the  nasal  operation,  she  evinced  a 
very  strong  objection  to  the  performance  of  cautery  of  the  mucosa,  and 
wished  first  to  try  vaccine  treatment. 

A  bacteriological  examination  showed  streptococcus,  both  longus 
and  hrevis,  and  M.  catavrhalis.     An  autogenous  vaccine  was  prepared. 

On  October  12th  inoculation  of  10  million  each  streptococcus  and 
25  million  M.  catavrhalis. 

On  October  2oth  she  presented  herself,  looking  much  better  and  less 
jaded,  and  reported  that  she  had  had  an  attack  on  the  second  and  sub- 
sequent nights,  with  the  exception  of  the  last  two,  when  she  had  been 
perfectly  free.     The  dosage  was  increased  by  one  half. 

October  27th  :  She  reported  that  on  the  night  of  the  inoculation 
and  that  following  she  had  had  attacks  of  moderate  severity,  but  since 
then  had  been  quite  free  from  any  but  very  mild  daily  attacks.  Repeated 
last  dosage. 

November  7th  :  Reports  a  bad  attack  on  night  of  October  27th  ; 
since  then  only  very  mild  daily  attacks.     Repeated  dosage. 


lOO  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

November  15th  :  Continued  improvement  in  general  health  ;  no  pro- 
nounced reaction  after  last  ;  very  slight  daily  attack.    Repeated  dosage. 

November  27th  :  Reports  a  bad  attack  on  night  of  23rd  due  probably 
to  indigestion,  otherwise  only  mild  daily  attack.     Repeated  dosage. 

December  6th  :  Had  a  bad  attack  on  night  of  November  28th ;  no 
others  by  day  or  night  till  morning  of  December  6th.    Repeated  dosage. 

December  15th :  A  very  slight  attack  on  night  of  December  gth  ; 
none  whatever  since  ;  double  initial  dosage  given. 

With  the  result  so  far  the  patient  was  delighted  and  I  more  than 
pleased ;  in  the  last  week  of  December  she  caught  the  prevailing  influenza 
epidemic,  swarms  of  the  bacilli  being  found  in  her  sputum  along  with 
some  pneumococci.  She  was  quite  prostrated,  and  as  the  asthmatic 
attacks  soon  recurred  with  all  their  old  violence,  recourse  had  to  be 
had  to  adrenalin  subcutaneously ;  this  controlled  the  severity  of.  the 
attacks  admirably,  but  seemed  to  have  no  influence  upon  their 
frequency.  A  fresh  vaccine  of  B.  influenzce  and  pneumococcus  was 
prepared  to  combine  with  the  streptococcsd-catarrhalis  one.  Doses 
of  the  combined  vaccines  were  given  on  January  8th,  17th,  27th, 
February  6th  and  19th,  but  the  infection  by  the  B.  infliienzce  proved 
very  hard  to  eradicate ;  even  when  this  was  apparently  done  the 
frequency  and  severity  of  the  asthmatic  attacks,  which  now  refused  to 
be  controlled  by  the  original  vaccines,  were  such  that  I  no  longer 
found  difficulty  in  persuading  the  patient  to  place  herself  in  Dr. 
Alexander  Francis's  hands;  she  now  informs  me  that  the  result  of  the 
cauterisation  has  been  entirely  satisfactory. 

The  unhappy  effect  of  infection  by  the  B.  influenzce  is  only  too  well 
shown  in  this  case. 

Case  2. — Mr.  B — ,  aged  50  years,  outdoor  telegraph  superintendent 
in  the  north  of  Scotland.  Weight  formerly  10  st.  6  lb.,  now  8  st.  6  lb. ; 
complains  of  chronic  bronchitis  with  spasmodic  asthma. 

History  was  as  follows  : 

January,  1909  :  Acute  attack  of  bronchitis,  lasting  for  six  weeks, 
then  recovery. 

January,  1910  :  Another  acute  attack  lasting  eight  weeks,  and 
leaving  behind  it  considerable  dyspnoea,  which,  by  June,  1910,  had 
assumed  a  spasmodic  form,  and  become  so  severe  that  he  was  incapable 
of  any  exertion.  On  September  17th  he  suddenly  recovered,  and 
remained  quite  well  till  January  3rd,  1911,  when  a  fresh  acute  attack 
of  bronchitis  supervened  ;  this  persisted  till  the  end  of  March,  by  which 
time  partial  recovery  was  established  ;  regular  attacks  of  spasmodic 
dyspnoea,  however,  continued,  and  in  September,  1911,  he  had  a 
bacteriological  examination  made  of  his  sputum,  and  a  vaccine 
containing  20  million  M.  catarrhalis  and  10  million  pneumococcus  was 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  lOI 

prepared,  but  not  by  me,  and  administered  at  intervals  of  two  to  four 
days.  Slight  immediate  improvement  in  the  direction  of  lengthening 
of  the  periods  of  freedom  from  dyspnoea  was  produced. 

September,  igii,  to  January,  1912  :  Patient  states  that  the  dys- 
pnceic  attacks  continued  with  great  regularity  at  an  average  interval 
of  nine  hours.  Minimum  interval,  four  hours ;  maximum,  twenty 
hours.  The  only  remedy  which  gave  any  certain  relief  was  adrenalin 
chloride  subcutaneously. 

At  the  end  of  January,  1912,  he  consulted  me  by  post  as  he  had 
long  been  unable  to  leave  the  house.  I  examined  the  sputum,  and 
found  Streptococcus  niaxiniiis  in  considerable  numbers,  and  a  few  M. 
catavrhalis  and  pneumococcus.  Informed  him  that  he  had  hardly  given 
the  previous  vaccine  a  fair  trial,  but  that  I  thought  I  could  compound 
one  rather  better  suited  to  his  needs  if  he  would  place  its  administra- 
tion in  the  hands  of  a  medical  man,  who  would  allow  me  to  direct 
treatment.  Dr.  K.  Gillies  kindly  undertook  the  task,  and  began 
treatment  with  an  initial  dosage  of  Streptococcus  maximns  25  millions, 
pneumococcus  25  millions,  and  M.  catavrhalis  50  millions. 

On  March  29th,  191 2,  I  received  a  report  from  the  patient  and 
make  the  following  abstracts:  "Prior  to  commencing  with  your 
vaccine  I  had  very  short  periods  of  freedom  from  dyspnoea,  and 
that  with  entire  rest  and  confinement  to  my  bed-room.  Now  you 
will  observe  I  have  much  longer  periods  of  ease  and  that  with  more 
movement  about.  These  have,  as  is  shown  on  the  chart,  been 
temporarily  affected  by  an}^  labour,  stress,  etc.  That  I  have  been  able 
to  get  out  at  all  this  cold  v/eather  shows  a  very  marked  improvement. 
My  appetite  is  good  considering  the  little  exercise,  my  flesh  is  clear 
and  more  ruddy,  and  my  weight  has  increased  6  lbs.  during  the  last 
eight  weeks.  My  sputum  is  becoming  very  scanty;  you  asked  me  to 
send  a  fresh  specimen  if  I  found  my  progiress  not  satisfactory.  I  do 
not  think  the  time  has  arrived  for  this  as  I  consider  I  am  so  very  much 
improved."  On  May  7th  I  received  a  fresh  report:  from  May  ist  to 
to  May  5th  inclusive  he  had  only  experienced  one  moderate  dyspnceic 
attack,  which  had  at  once  yielded  to  a  small  dose  of  adrenalin  chloride. 
By  this  time  Dr.  Gillies  had  increased  the  dosage  of  vaccine  to  ten  times 
the  initial  one,  and  doses  of  even  this  magnitude  failed  to  excite  a 
dyspnoeic  attack.  A  rough  idea  of  the  progress  of  the  case  may  be 
gathered  from  Chart  XII. 

In  order  to  arrive  at  a  just  appreciation  of  the  result  it  must  be 
remembered,  as  the  patient  saj'S,  that  after  a  long  period  of  complete 
confinement  to  his  room,  he  was  at  the  time  of  the  report  indulging  in 
considerable  out-door  exercise  at  a  most  trying  period  of  year  to  all 
asthmatics. 


I02  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

In  conclusion  I  would  merely  say  that  although  many  of  my  cases 
have  pursued  more  favourable  courses  than  these  two,  it  is  yet  impos- 
sible for  me  to  dogmatise  at  all;  it  must  suffice  to  state  that  within  my 
experience  much  good  may  accrue  to  asthmatic  cases  by  a  course  of 
vaccine  treatment,  but  that  with  this  disease  more  than  with  any  other 
each  case  must  be  considered  apart  and  treated  on  its  own  merits,  not 
according  to  any  given  procedure  or  rule  of  thumb. 


CHAPTER   VIII. 
VACCINES    IX    PNEUMONIA. 

Definition. —  Pneumonia  typically  is  an  acute  febrile  disease,  begin- 
ning as  a  rule  suddenly  but  sometimes  insidiously,  associated  with 
massive  consolidation  of  the  lung,  running  a  fairly  definite  course,  and 
terminating  within  ten  days  by  crisis  or  lysis.  Inasmuch,  however, 
as  the  course  is  sometimes  less  definite,  the  term  is  taken  to  include  all 
cases  of  acute  febrile  disease  accompanied  by  massive  consolidation  of 
the  lung. 

Etiology. — While  it  is  undoubtedly  true  that  pneumonia  is  a  disease 
characterised  especially  by  sudden  onset,  I  think  that  in  a  considerable 
proportion  of  cases  of  true  lobar  pneumonia  it  would  be  more 
accurately  regarded  as  an  acute  exacerbation  in  a  chronic  infection  by 
the  pneumococcus  of  the  bronchial  or  pulmonary  tissues,  an  infection 
which  originally  took  its  rise  in  an  acute  pneumococcal  infection 
of  the  upper  respiratory  passages,  and  subsequently  invaded  those  of 
the  chest,  giving  rise,  perhaps,  to  nothing  more  than  a  bronchial 
catarrh,  which  apparently  cleared  up  more  or  less  completeh-.  As  I 
have  already  mentioned  previously  I  have  had  the  opportunity  of 
watching  several  such  cases,  some  for  several  years,  and  of  making 
periodic  examinations  of  the  sputum,  which  may  be  extremely  scanty, 
and  of  noting  with  what  extreme  tenacity  the  pneumococci  retain 
their  hold  upon  the  tissues.  In  some  instances  the  most  patient 
treatment  by  means  of  vaccines  and  otherwise  fails  to  dislodge  them 
completely. 

On  page  193  of  No.  7,  vol.  i,  of  the  Journal  of  Vaccine  Therapy,  Dr. 
Graham  Morris  tells  his  own  stor}-,  which  illustrates  well  this  tendency 
of  the  pneumococcus  to  persist  in  the  pulmonary  tissues. 

I  do  not  for  a  moment  mean  that  all  attacks  of  acute  pneumonia 
are  due  to  a  lighting  up  into  virulence  of  pneumococci  long  dormant  in 
the  pulmonary  tissues  ;  in  some  instances  an  acute  nasal  or  tracheal 
catarrh  rapidly  tracks  down  into  the  chest,  especially  when  the 
B.  influenzcs  is  associated  with  the  pneumococcus,  and  sets  up  an  attack 


104  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

of  acute  pneumonia  in  those  who  apparently  have  not  suffered  for  many 
years  from  any  catarrhal  affection  of  the  chest ;  while  yet  again,  and  in 
perhaps  the  majority  of  cases,  the  pneumonic  attack  is  not  preceded 
by  any  obvious  catarrh  of  the  upper  respiratory  passages.  This  is 
entirely  a  question  of  local  immunity.  I  have  just  seen  a  patient  from 
Guatemala,  who  tells  me  that  every  year  there  is  a  pneumonia 
epidemic  of  exceptional  virulence ;  he  himself  and  others  of  his 
acquaintance  have  never  fallen  victim,  but  are  affected  by  very  severe 
recurrent  catarrhs  of  the  upper  passages  ;  in  his  case  these  are  entirely 
confined  to  the  nose  and  post-nasal  space.  From  these  parts  I  have 
taken  cultures  and  found  thousands  of  pneumococci  in  each  loopful  of 
mucus  ;  with  him  the  resistance  of  the  pulmonary  tissues  is  obviously 
very  high,  whereas  with  many  hundreds  of  the  natives  it  is  correspond- 
ingly low. 

Of  this,  however,  I  am  absolutely  convinced,  that  in  the  United 
Kingdom  the  percentage  of  cases  in  which  the  pneumococcus  persists 
in  the  lung  after  merely  causing  an  acute  bronchial  catarrh  is  very 
much  greater  than  is  commonly  imagined,  and  that  their  presence 
there  is  fraught  with  danger  to  the  host.  The  consideration  of  this 
question  will  be  resumed  later. 

Bacteriology.' — Until  recently  the  pneumococcus  of  Frankel  was 
regarded  as  the  specific  and  only  cause  of  acute  pneumonia ;  it  is  now 
known  that  other  bacteria  are  capable  of  setting  up  this  condition, 
either  alone  or  in  combination  with  each  other  or  associated  with  the 
pneumococcus  ;  in  the  last  instance  doubt  is  cast  upon  their  getiological 
significance.  It  is  otherwise  when  they  occur  alone,  and  it  must  be 
granted  that  the  following  may  be  responsible :  Friedlander's  pneumo- 
bacillus,  B.  influenzcB,  Streptococcus  mitcosus,  staphylococcus,  B.  typJwsus, 
B.  coli.     Some  of  these  I  propose  to  mention  a  little  in  detail. 

"  Friedlander  "  pnetimonia  was  first  described  by  Philippi  {Munch, 
vied.  Woch.,  1902),  later  by  Lenhart2  (N othnageV s  Spezielle  Path,  und 
Therapie,  Bd.  iii),  by  Apelt  {Munch,  med.  Woch.,  1908,  p.  833),  and  by 
others,  while  Stiihlern  {Zentral.  filr  Bakt.,  Bd.  xxxvi,  1904)  carefully 
studied  forty-five  cases,  and  Kokawa  {Deut.  Archiv  fur  klin.  Med., 
1904)  eighteen  cases,  and  Cordier  Badolle  and  Brissaud  (Lyon  Med., 
April  14th,  1912)  have  recently  reviewed  the  whole  subject  of  Fried- 
lander  pneumonia.  These  authorities  all  agree  that  there  is  a  distinct 
form  of  pneumonia  due  to  this  bacillus,  characterised  by  the  great 
formation  of  mucus  in  the  infiltrated  areas,  by  the  surface  of  the  lung 
being  sometimes  covered  with  slimy  exudate,  by  the  imperfect  develop- 
ment of  "  redhepatisation,"  this  having  a  grey  to  black  appearance,  by 
the  absence  of  marked  fibrinous  exudate  and  of  hemorrhage.  On  the 
other  hand  there  is  a  great  tendency  to  massive  blood  infection  and  to 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  IO5 

the  disease  running  a  malignant  course  :  while  suppuration  and  abscess 
formation  are  especially  liable  to  occur.  The  distribution  may  be 
either  lobar  or  lobular. 

Streptococcus  pneumonia  appears  to  be  almost  indistinguishable  from 
the  pneumococcal  variety,  beginning,  like  it,  with  a  rigor  or  pleuritic 
pain,  and  being  associated  with  herpes  labialis.  The  pyrexia,  however, 
tends  to  be  intermittent,  and  may  persist  for  a  considerable  time,  while 
the  physical  signs  may  be  those  of  broncho-pneumonia.  Filarelow  has 
described  four  such  cases,  and  Schottmuller  {Munch,  nied.  Woch.,  1903, 
p.  1427)  six  in  which  it  was  lobar  in  type. 

TypJwid  pneumonia  is  regSLided  by  some  authorities  as  nothing  else 
than  a  pneumococcal  pneumonia  occurring  during  the  course  of 
typhoid  fever,  in  which  the  presence  of  the  pneumococcus  is  over- 
shadowed by  the  B.  typhosus,  the  latter  being  nothing  more  than  a 
secondary  invader.  With  the  statement  that  the  pneumococcus  is 
always  present  in  such  cases  I  am  not  prepared — perhaps  on  insufficient 
grounds — to  agree.  In  a  case  of  typhoid  pneumonia  which  I  have 
recorded  {Vaccine  Therapy,  Edit.  3,  p.  158)  the  bacteriological  findings 
were  B.  typhosus  and  a  few  Streptococcus  longus.  The  immediate  good 
result  produced  on  the  lung  condition  by  an  inoculation  of  an  auto- 
genous typhoid  vaccine  would  appear  to  show  that  this  organism  was 
the  important  aetiological  factor. 

Influenza  pneumonia  is  worthy  of  much  more  study  than  has  been 
accorded  to  it.  The  pneumonia  supervening  on  an  attack  of  so-called 
"  influenza,"  this  latter  being  much  more  frequently  a  pure  pneumo- 
coccal or  a  combined  pneumococcal  and  influenzal  infection,  is  com- 
monly regarded  as  a  fresh  superimposed  infection  by  the  pneumococcus  ; 
this  is  an  utterly  erroneous  view  in  the  great  majority  of  cases.  On 
the  other  hand,  a  true  B.  influenzce  infection  of  the  respiratory  tract  does 
sometimes  culminate  in  a  pneumonia ;  this  pneumonia  may  be  due  to 
a  fresh  infection  by  the  pneumococcus,  but  occasionally  the  infection 
remains  a  pure  B.  influenzcs  one.  I  have  only  seen  two  such  cases;  the 
type  was  broncho-pneumonic,  and  was  characterised  by  prolonged  high 
pyrexia,  great  constitutional  depression  and  a  malignant  course,  each 
case  ending  as  one  of  lung  abscess. 

I  have  entered  into  this  aspect  of  pneumonia  somewhat  fully  for  the 
following  reason,  When  some  years  ago  I  suggested  that  for  immunis- 
ing purposes  a  vaccine  of  the  various  paratyphoid  organisms  should  be 
combined  with  the  ordinary  typhoid  vaccine  I  was  derided  by  several 
critics  ;  the  careful  work  that  has  since  been  done  shows  that  the  pro- 
portion of  cases  diagnosed  as  typhoid  fever  which  are  really  ones  of 
paratyphoid  fever  is  in  some  localities  and  in  some  epidemics  anything 
but   negligable ;    in  one  instance  10  per  cent,  and   in  another  25  per 


Io6  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

cent,  of  the  cases  were  found  to  be  in  reality  paratyphoid  fever.  In  the 
same  way  I  feel  sure  that  accurate  bacteriological  examinations  would 
show  that  the  percentage  of  cases  of  pneumonia  due  to  bacteria  other 
than  the  pneumococcus  is  considerably  greater  than  is  supposed.  From 
the  purely  clinical  aspect  this  may  not  be  of  great  import  ;  to  those  who 
contemplate  the  routine  treatment  of  pneumonia  with  vaccines  it  is  a 
matter  of  considerable  importance. 

This  leads  me  to  a  brief  consideration  of  the  methods  whereby  a 
correct  bacteriological  diagnosis  may  be  made.  There  are  three  chief 
ones,  viz.  (i)  sputum  examinations,  (2)  blood  examinations,  (3)  lung 
puncture  observations. 

To  the  essential  precautions  which  must  be  observed  in  the  collection 
of  sputum  for  the  purposes  of  a  bacteriological  examination  I  have 
already  referred  on  several  occasions.  The  due  observance  of  these  will 
tend  greatly  to  diminish  the  difficulties  experienced  by  many  observers. 
While  it  is  true  that  sputum  may  be  very  scanty  or  even  absent  in  the 
first  day  or  two  of  the  pneumonic  attack,  this  is  not  often  the  case  ;  a 
very  small  quantity  indeed  will  suffice,  and  careful  insemination  thereof 
on  blood-agar  plates  will  almost  invariably  lead  to  the  ready  isolation  of 
the  pneumococci  or  other  organisms,  no  matter  how  few  these  may  be. 
At  the  same  time  if  no  sputum  be  obtainable  or  a  hasty  examination  of 
a  stained  film  leads  to  anticipation  of  failure  blood  culture  should  be  at 
once  resorted  to  ;  10  to  15  c.c.  of  blood  should  be  withdrawn  from  a  vein 
of  the  arm  with  due  precautions ;  i  c.c.  should  be  spread  over  the 
surface  of  an  agar  plate,  the  balance  introduced  into  100  c.c.  of  dextrose 
peptone  broth.  The  failure  of  some  observers  to  secure  more  than  25 
per  cent,  of  positive  blood-cultures  I  believe  to  be  due  (i)  to  the  em- 
ployment of  too  little  blood — at  least  10  c.c.  should  be  taken  ;  (2)  to 
the  insufficient  dilution  of  the  blood  with  culture  fluid — the  blood  should 
be  diluted  eight  to  ten  times ;  (3)  to  the  use  of  ordinary  broth  instead 
of  broth  containing  2  per  cent,  dextrose.  Occasionally  incubation  has 
to  be  continued  for  forty-eight  hours,  but  this  is  very  rarely  so.  Some 
observers  have  obtained  positive  blood  cultures  in  80  per  cent,  of  cases, 
and  it  would  appear  that  there  is  in  the  first  few  days  a  true  bacteriasmia  ; 
in  the  case  of  "  Friedlander  "  and  "  typhoid  "  pneumonia  vast  numbers 
of  the  bacteria  may  be  present  in  the  blood. 

The  procedure  for  lung  puncture  I  have  already  described  on  p.  10. 

By  a  judicious  combination  of  these  methods  I  believe  that  a  reliable 
diagnosis  of  the  true  infective  agent  may  be  made  in  every  case  without 
exception. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  lO/ 

Tlie  Prophylaxis  of  Pneumonia. 

If  the  view  I  have  already  enunciated  as  to  the  manner  in  which 
many  cases  of  acute  pneumonia  originate  be  correct,  it  at  once  follows 
that  no  case  of  respiratory  catarrh  due  to  the  pneumococcus,  B. 
influenzcB,  streptococcus  or  B.  of  Friedlander  is  to  be  lightly  regarded  or 
to  be  considered  as  cured  so  long  as  there  is  any  sputum  in  which  the 
organism  can  be  discovered,  or  so  long  as  any  physical  signs  persist  in 
the  chest.  Treatment  by  means  of  vaccines  must  be  continued  until 
complete  disappearance  of  the  infection  is  secured ;  and  if  this  cannot 
be  effected,  as  will  sometimes  prove  to  be  the  case,  then  the  patient's 
immunity  must  be  maintained  at  as  high  a  level  as  possible  by  the 
administration  of  two  or  three  fall  doses  of  vaccine  at  seven-day 
intervals,  say,  every  four  months. 

I  have  in  this  way  kept  entirely  free  from  all  catarrhal  attacks  during 
the  past  three  years  a  well-known  personage  who  first  consulted  me  at 
the  age  of  eighty-four.  His  pneumococci  have  never,  so  far  as  I  know, 
entirely  gone,  and  I  have  considered  it  my  duty  to  warn  him  that 
sooner  or  later  they  will  make  their  presence  felt  if  he  allows  his 
immunity  to  fall  unduly. 

Another  important  point  in  such  cases  is  that  the  factor  which, 
above  all,  probably  decides  the  lighting  into  virulence  of  the  dormant 
pneumococci  is  the  incidence  of  a  fresh  infection  by  some  other  catarrhal 
micro-organism  ;  chief  among  these  is  undoubtedly  the  B.  infliienzce, 
probabl}-  also  the  streptococcus  and  M.  catarrhalis,  and  it  is  owing  to  this 
fact  that  an  epidemic  of  influenza  is  nearly  always  attended  by  a  greatly 
raised  m.ortality,  due  to  acute  pneumonia.  At  the  same  time  it  must  be 
admitted  that  a  pure  invasion  of  any  part  of  the  respiratory  tract  by 
the  B.  infliLenzcE  is  comparatively  rare  ;  there  is  nearly  always  some  other 
associated  microbe  and  this  is  usually  the  pneumococcus,  so  that  a 
certain  percentage  of  the  cases  of  pneumonia  encountered  during  a  so- 
called  influenza  epidemic  are  really  due  to  a  fresh  infection  by  the 
pneumococcus  associated  with  the  B.  influenzcs.  In  such  cases  the 
employment  of  the  suitable  vaccine  in  the  first  stages  of  the  infection 
before  the  bacteria  have  actually  located  themselves  in  the  pulmonary 
tissues  would,  I  venture  to  affirm,  almost  entirely  prevent  the  onset 
of  pneumonic  attacks,  and  many  valuable  lives  would  thus  be  saved 
at  every  such  epidemic. 

The  Pathology  of  Acute  Pnetnnonia  and  its  Bearing  on  Vaccine 

Treatment. 

Before  it  is   possible   to  use   vaccines   in  this   condition  with  any 
prospect  of  achieving  thoroughly  satisfactory  results,  it  is  essential  to 


io8 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


have  a  perfectly  clear  idea  of  the  pathology  of  the  disease  and  how 
recovery  is  brought  about. 

In  the  first  stage,  that  of  congestion,  the  capillaries  are  dilated  and 
tortuous  from  distension  with  blood;  the  air-cells  are  net  as  yet 
completely  airless,  but  are  more  or  less  filled  with  frothy  reddish 
serum  albumen ;  the  supply  of  opsonin  and  other  anti-bodies  in  the 
circulating  fluids  is  below  the  normal,  the  leucocytes  as  a  rule 
considerably  above  the  normal. 

During    the    second    stage,  known    as    red    hepatisation    from   the 

Chart  XIII. 


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Relation  between  Leucocytes,  Opsonic  Index,  and  Temperature  in  a  Case 

OF  Pneumonia  (Eyre). 

Dotted  line    =    number    of    leucocytes  per    cubic  millimetre  ;    thick    line    =   opsonic 

index  ;  thin  line  =  temperature. 

resemblance  which  the  lung  then  bears  to  the  liver,  the  organ  is  of  a 
dull  red  colour,  finely  granular  in  section,  completely  airless,  solid,  and 
sinks  in  water.  The  contents  of  the  alveoli  consist  of  coagulated 
fibrin  which  holds  in  its  meshes  red  blood-cells,  leucocytes,  exfoliated 
epithelium  and  bacteria.  Although  the  capillaries  are  much  com- 
pressed, they  for  the  most  part  remain  pervious.  The  supply  of  anti- 
bodies remains  low,  and  the  leucocytes  in  the  circulating  blood  have 
fallen  considerably,  although  they  may  still  be  above  the  normal ;  this 
fall  may  be  due  to  the  vast  numbers  stored  up  in  the  pulmonary  tissues. 
The  stage  of  red  hepatisation  passes  into  that  of  grey  hepatisation, 
the  change  of  colour  being  brought  about  by  the  extravasated  red 
corpuscles  losing  their  haemoglobin,  by  the  stasis  of  the  circulation 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


lOQ 


through  the  capillary  vessels  of  the  alveoli,  and  by  the  increased 
number  of  leucocytes  which  crowd  the  air-cells  and  alveolar  walls;  the 
leucocytes  in  the  blood-stream  have  now  fallen  to  their  minimum. 

In  cases  which  pursue  a  normal  course,  this  stage  of  "  grey 
hepatisation  "  so  rapidly  passes  into  that  of  "  resolution  "  that  it  may 
be  regarded  as  the  stage  of  commencing  resolution;  the  leucocytes  and 
exfoliated  epithelium  undergo  granular  and  fatty  degeneration,  the 
fibrin  softens  and  is  absorbed,  the  capillary  circulation  becomes  actively 
re-established,  the  alveoli  again  contain  air,  and  the  alveolar  epithelium 

Chart  XIV. 
Days  of  disease 

I     2    S    4     5    6    7     3    9    so    n    E2   SS   t4-   fa 


•7 
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•S 
•2 

Types   of    Reaction    of   the    Opsonic    Index    in    Pneumococcic  Infection 

(after  Eyre). 

(rt)   Immediate  rise  as  seen  in  mild  infections  ;   (6)  delayed  rise  ;    (c)  progressive 

decline  as  seen  in  severe  and  fatal  infections. 

is  regenerated.  The  commencement  of  this  process  of  resolution 
would  appear  to  coincide  in  point  of  time  with  the  sudden  fall  of 
temperature,  occurring  in  nearly  50  per  cent,  of  cases,  known  as  the 
"crisis,"  and  with  the  sudden  rise  of  leucocytes  and  immune  bodies  in 
the  general  blood-stream.  The  annexed  chart,  No.  13,  of  Dr.  Eyre"s 
shows  well  the  relationship  between  temperature,  leucocytes  and  opsonic 
index  at  the  various  stages  of  the  attack ;  while  chart  No.  14  shows  the 
course  of  the  opsonic  index  in  cases  {a)  in  which  the  fall  of  temperature 
is  by  crisis,  {h)  where  it  is  by  lysis,  (c)  where  the  case  proceeds  to  a 
fatal  issue. 

The  chief  factors  concerned  in  the  processes  of  cure  are  (i)  leuco- 
cj'tes,  (2)  endothelial  cells  of  the  alveoli,  (3)  opsonins,   (4)  antitoxins, 


no  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

agglutinins  and  other  immune  bodies.  As  we  have  seen  above,  the 
opsonic  index  yields  a  very  fair  indication  of  the  progress  of  immunity, 
and  the  extinction  of  the  infective  agents  would  appear  to  depend 
largely  upon  the  action  of  opsonin  which  is  chiefly  of  the  thermolabile 
variety.  The  phagocytosis,  however,  is  not,  as  might  be  supposed, 
carried  out  in  the  main  by  the  polymorphonuclear  leucocytes,  which,  as 
we  have  seen,  have  so  largely  increased  in  numbers  at  or  just  before  the 
crisis,  but,  as  De  Jong  has  pointed  out,  by  the  endothelial  cells  of  the 
alveoli,  many  of  which  become  transformed  into  macrophages.  The 
chief  role  of  the  leucocytes  would  appear  to  be  the  formation  and 
excretion  of  ferment  for  the  solution  of  the  fibrin  filling  the  alveolar 
cells;  this  would  appear  to  be  the  explanation  of  the  great  storing  up 
of  leucocytes  in  this  locality. 

It  is  now  well  recognised  that  the  rapid  respiration  and  high  tem- 
perature so  characteristic  of  pneumonia  are  due  to  a  poisoning  of  the 
nerve-centres  by  the  endotoxins  liberated  by  the  death  of  the  pneu- 
mococci,  this  same  agent  being  also  responsible  for  changes  in  the 
musculature  and  nerve  control  of  the  heart,  which  may  lead  to 
circulatory  failure  even  when  convalescence  appears  to  have  been 
well  begun.  The  satisfactory  elaboration  of  the  corresponding  anti- 
bodies is  therefore  a  very  essential  factor  for  recovery,  and  the  pro- 
duction of  the  "crisis"  is  dependent  upon  the  elaboration  of  such 
antibodies,  which  appear  to  be  inoperative  until  they  reach  a  certain 
concentration  ;  in  such  cases  it  seems  that  the  reaction  between  toxin 
and  anti-toxin  must  be  "  all  or  nothing,"  and  so  bears  no  resemblance 
to  the  neutralisation  "in  vitro'''  of  diphtheria  toxin  by  antitoxin.  In  cases 
where  recovery  is  by  lysis  the  neutralisation  must  be  more  gradual. 

Let  us  now  consider  what  bearing  these  various  facts  have  upon 
the  application  of  vaccine  treatment  to  this  disease.  Our  objective 
must  be  a  two-fold  one — to  kill  the  bacteria  and  to  neutralise  their 
toxin.  The  question  is,  Are  these  possible  of  attainment  ?  The  answer 
is,  This  depends  largely  on  the  stage  of  the  disease,  the  virulence  of  the 
infection  and  the  responsive  powers  of  the  individual. 

In  the  stage  of  pulmonary  congestion  the  bacteria  are  circulating  in 
the  blood-stream,  and  are  present  in  but  scanty  numbers  in  the 
pulmonary  tissues  ;  the  resisting  power  of  the  body  has  been  obviously 
broken  down,  and  bacteria  circulating  in  the  blood-stream  do  not 
appear  to  be  capable  of  leading  to  the  elaboration  of  antibodies  ; 
there  is  thus  both  a  local  and  general  defect  of  these,  but  at  the  same 
time  the  amount  of  toxin  formed  is  not  considerable.  If,  therefore,  the 
bacteria  could  be  exterminated  the  disease  process  would  be  ended.  It 
is  now  well  recognised  that  the  introduction  into  healthy  subcutaneous 
or  muscle  tissues  of  a  therapeutic   dose  of  vaccine   will  lead  to  the 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  I  I  I 

speed}^  elaboration  of  the  corresponding  antibodies.  A  vaccine  of 
pneumococci  is  but  slightly  toxic,  and  its  administration  leads  to  the 
elaboration  of  considerable  amounts  of  opsonin,  which  is  chiefly  of  the 
thermostable  variety,  and  of  a  small  amount  of  antitoxin.  The  fact 
that  this  is  precisely  what  is  then  required  is  the  strongest  possible 
argument  for  the  employment  of  a  vaccine  at  the  very  inception  of  the 
attack.  It  is  true  that  the  virulence  of  the  infection  then  is  high,  but 
so  is  the  responsive  power  of  the  individual.  Unfortunately  there  are 
two  obstacles  to  this  procedure:  (i)  the  fact  that  the  opportunity  does 
not  always  present  itself,  many  cases  not  being  seen  till  the  disease  pro- 
cesses are  further  advanced  ;  (2)  the  refusal  of  medical  men  to  re- 
cognise every  case  of  pneumonia  as  potentially  a  fatal  one. 

When  consolidation  has  occurred  bacteria  are  still  often  to  be  found 
in  the  blood-stream,  but  their  multiplication  in  the  pulmonary  tissues 
has  much  advanced  :  here  they  are  enclosed  in  a  meshwork  of  fibrin, 
in  a  warm  nidus  admirably  suited  to  their  growth  ;  the  blood  and  lymph 
supply  being  more  or  less  in  a  state  of  stasis,  even  if  the  amount  of 
immune  bodies  in  the  body  generally  is  niore  than  adequate  these  are 
not  available,  or  only  to  a  limited  extent.  No  immediate  material  good 
might  therefore  be  anticipated  from  increasing"  them  by  means  of  a 
therapeutical  inoculation ;  that  good  does  sometimes  result  therefrom 
is  due  to  the  fact  that  all  portions  of  the  infected  lung  are  not  in  the 
same  stage ;  one  area  may  be  in  a  state  of  congestion,  another  in  that 
of  red  hepatisation,  and  yet  a  third  in  that  of  commencing  resolution. 
The  main  objective,  therefore,  is  to  relieve  the  strain  on  the  heart's 
musculature  as  much  as  possible  by  lowering  the  viscosity  of  the  blood 
with  full  doses  of  citric  acid,  by  dilating  the  blood-vessels  locally  by 
the  application  of  heat,  etc.,  and  by  relieving  the  general  blood-pressure 
by  promoting  free  diaphoresis  and  action  of  the  bowels,  and  if  necessary 
by  bleeding.  At  the  same  time  we  may  increase  the  amount  of  anti- 
bodies, both  antitoxic  and  antibacterial,  and  the  number  of  leucocytes 
against  the  time  when  commencing  resolution  may  enable  them  to  be 
carried  to  the  battle  front.  Resolution  wall  inevitably  entail  the  free 
liberatian  into  the  re-established  circulation  of  quantities  of  toxin  which 
have  been  stored  up  in  the  consolidated  tissues ;  hence  it  is  very  im- 
portant now  to  ensure  that  the  leucocytes  and  various  antibodies  can 
reach  the  infected  areas  with  the  least  possible  difficulty,  and  to  preserve 
the  heart  musculature  as  much  as  possible  from  the  action  of  the 
bacterial  toxins.  Were  a  really  reliable  antitoxic  serum  available  for 
the  neutralisation  of  the  toxins,  the  combination  of  serum  and  vaccine 
could  hardly  fail  to  prove  of  the  utmost  value  during  this  period  of 
resolution.  Unfortunately  the  best  available  sera,  Romer's  and  Pane's, 
appear  to  leave  much  to  be  desired ;  their  defects  may,  however,  be 


I  1 2  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

more  apparent  than  real,  failures  with  them  being  perhaps  as  much 
due  to  their  improper  use — viz.  insufficient  dosage  and  non-systemic 
administration — as  to  any  intrinsic  imperfections. 

The  administration  of  a  vaccine  when  resolution  is  impending  will 
prove  of  immediate  service  provided  that — 

(i)  The  supply  of  anti-bacterial  bodies  is  otherwise  insufficient. 

(2)  The  tissues  are  capable  of  responding  to  stimulation,  and  this 
they  almost  invariably  are. 

(3)  The  heart  mechanism  is  sufficiently  strong  to  withstand  the 
attack  of  the  toxins  so  copiously  liberated  during  this  stage. 

As  we  have  seen,  the  production  of  the  "  crisis  "  is  due  to  the  massive 
neutralisation  of  toxin  by  antitoxin.  Hence  it  is  that  a  small  dose  of 
vaccine  may  at  one  time  suffice  to  produce  an  immediate  reaction  as 
evidenced  by  crisis  occurring  and  at  another  time  may  appear  to  fail. 
The  power  of  a  vaccine  to  stimulate  the  formation  of  antitoxin  is  but 
slight ;  hence  if  the  defect  in  antitoxin  is  small  the  addition  of  a  small 
quantity  will  suffice,  but  if  the  defect  be  great  a  much  increased  dose 
of  vaccine  may  fail  to  produce  the  additional  amount  requisite  to  make 
good  the  considerable  defect ;  the  total  amount  of  antibody  then  present 
being  the  sum  of  the  amounts  produced  so  far  by  natural  means  plus 
the  amount  produced  b\^  the  inoculation  of  the  vaccine  requires  further 
supplementing,  either  by  the  natural  response  of  the  body  to  the 
infection  or  to  the  stimulation  of  another  dose  of  vaccine,  or  by  both 
these  means. 

As  has  been  already  mentioned,  when  the  fall  of  temperature  is  by 
lysis  this  massive  neutralisation  of  toxin  would  not  appear  to  occur, 
and  it  is  worth}^  of  note  that  the  proportion  of  cases  in  which  "  lysis  " 
occurs  rather  than  "  crisis  "  appears  to  be  greater  in  vaccinated  than  in 
unvaccinated  cases. 

These  conclusions  may  be  briefl}^  summarised  as  follows : 

(i)  The  administration  of  a  vaccine  in  the  earliest  stages  of  a 
pneumonic  attack  can  hardly  fail  to  be  productive  of  good  in  a  very 
considerable  percentage  of  cases,  for  thereby  is  ensured  the  formation 
of  adequate  bactericidal  bodies,  and  these  are  precisely  those  which  are 
of  service  at  this  period  of  the  disease. 

(2)  The  administration  of  a  vaccine  during  the  period  of  consolida- 
tion theoretically  can  hardly  be  productive  of  immediate  good,  but  the 
resultant  immune  bodies  may  prove  of  considerable  service  once 
"  resolution  "  has  begun.  Owing,  however,  to  the  fact  that  the  stage 
of  the  disease  may  vary  considerably  at  different  foci,  the  good  resulting 
from  vaccine  treatment  may  be  much  greater  than  might  be  anticipated. 
I  cannot  help  feeling  that  these  are  the  cases  where  the  fall  of  tempera- 
ture is  by  "  lysis." 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  I  1 3 

(3)  The  administration  of  a  vaccine  during  the  period  of  resolution 
will  prove  of  service  especially  if  resolution  be  delayed,  and  if  the 
supply  of  bactericidal  bodies  be  otherwise  insufficient. 

It  must,  however,  be  clearly  borne  in  mind  that  no  vaccine  treat- 
ment will  prove  of  service  unless — 

(i)  The  vaccine  be  the  proper  one  and  be  properly  prepared. 
It  is  no  use  employing  a  pneumococcal  vaccine  in  a  streptococcal 
or  Friedlander  infection,  nor  is  it  any  use  employing  a  vaccine  devoid 
of  immunising  properties.  I  have  already  mentioned  that  some  strains 
of  pneumococci  yield  a  good  vaccine  only  when  heat  is  used  to  ensure 
sterility,  others  only  when  sterilised  with  antiseptic. 

Experience  has  also  shown  that  an  autogenous  vaccine  is  preferable 
to  a  stock  one,  but  there  is  much  to  be  said  in  favour  of  beginning 
treatment  immediately  with  a  stock  polyvalent  vaccine  of  proved 
immunising  powers.  While  some  avirulent  strains  of  the  B.  diphthericB 
yield  the  most  potent  antitoxin,  and  some  strains  of  the  B.  typhosus  of 
very  low  virulence  the  most  powerful  vaccine,  with  the  pneumococcus 
the  more  highly  virulent  the  strain  as  a  rule  the  more  potent  is  the 
vaccine.  The  pneumococci  isolated  from  a  given  case  of  pneumonia 
may  vary  much  in  virulence  amongst  themselves ;  it  is,  therefore, 
obvious  that  in  the  preparation  of  an  autogenous  vaccine,  cultures 
should  be  taken,  not  from  one,  but  from  numerous  colonies. 
(2)  That  adequate  dosage  be  employed. 

Two  things  that  have  especially  struck  me  in  reading  the  clinical 
histories  of  cases  reported  by  those  who  have  failed  to  secure  satisfactory 
results  have  been — {a)  the  inadequate  dosages  :  for  instance,  in  the 
record  of  nineteen  cases  by  one  observer  I  find  that  nine  cases  did  not 
receive  a  dose  of  even  5  millions,  and  only  one  case  a  dose  of  25 
millions ;  this  is  little  more  than  playing  with  vaccine  treatment. 

(b)  The  tendency  to  reduce  subsequent  dosages  when  the  patient 
fails  to  make  any  response  to  a  first  dose,  which,  in  fact,  was  itself  quite 
an  inadequate  one  judged  b}^  the  experience  of  all  those  who  have 
achieved  good  results.  Failure  to  respond  in  any  way  to  a  given 
dosage  is  an  indication,  not  for  reduced,  but  for  increased  subsequent 
doses. 

I  might  also  add  that  increased  toxemia  has  been  at  times  regarded 
either  as  a  bad  effect  or  as  indication  for  diminished  dosage — in  reality 
it  may  be  neither.  It  is  an  indication  for  promoting  neutralisation  and 
excretion  of  the  toxins  by  every  available  means,  and  it  may  also  be 
indicative  of  hastening  resolution  and  consequent  increased  absorption 
of  the  toxins  into  the  general  circulation,  but  it  certainly  is  not  indica- 
tive of  postponing  further  inoculation  or  of  diminishing  the  dosage  :  is 
may  be  so  in  the  case  of  some  infections,  but  above  all,  is  this  not  the 


I  1 4  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

case  with  pneumococcal  infections  ?  The  toxic  contents  of  a  pneumo- 
coccal vaccine  are  so  small  that  the  amount  so  introduced  into  hea  thy 
tissues  is  without  effect  on  the  circulating  mass,  and  only  leads  to  the 
elaboration  of  the  corresponding  antitoxin,  while  the  stimulus  to  the 
formation  of  opsonin,  and  so  to  the  phagocytosis  of  the  bacilh  and 
neutralisation  within  the  macrophages  and  polynuclear  cells  of  their 
endotoxins,  is  very  great.  Personally,  I  have  never  seen  a  pneumo- 
coccal vaccine  do  any  injury  to  a  patient ;  per  contra  I  have  seen  several 
cases  of  persistent  hyperpyrexia  with  low  muttering  delirium,  one  or 
two  apparently  comatose,  make  almost  immediate  response  to  an 
inoculation  of  25  or  50  millions — it  is  true  that  these  were  cases  with 
marked  bacteriasmia,  but  this  I  think  they  often  are. 

In  conclusion,  I  will  briefly  summarise  the  procedure  which  has 
been  found  by  most  experienced  observers  to  be  the  best,  and  give  a 
short  resume  of  the  results  they  have  obtained. 

Procedure. 

(i)  Take  sputum  smears  and  cultures :  if  in  early  stage  blood- 
cultures,  if  in  advanced  stage  perform  a  lung  puncture,  and  proceed  to 
preparation  of  an  autogenous  vaccine. 

(2)  Immediately  administer  a  dose  of  not  less  than  25  millions  of  a 
polyvalent  stock  vaccine,  prepared  from  virulent  strains  and  of  proved 
immunising  power. 

(3)  If  no  definite  response  within  thirty-six  to  forty-eight  hours, 
repeat  above  dose  of  stock  vaccine,  or  preferably  of  the  autogenous 
vaccine  if  this  be  ready. 

(4)  If  still  no  response,  administer  double  the  above  dose  in  thirty- 
six  to  forty-eight  hours  ;  if  response,  as  evidenced  by  improved  clinical 
signs   and  symptoms  and  increased   well-being   of  the   patient,   defer- 
re-inoculation  for  three  days,  or  until  the  first  signs  of  retrogression  in 
the  general  condition  or  clinical  signs  and  symptoms. 

(5)  Maintain  dosage  or  even  increase  it,  and  continue  inoculations 
at  intervals  of  three  to  four  days,  until  the  patient  is  perfectly  well. 

(6)  If  the  patient  at  any  time  takes  a  sudden  turn  for  the  worse, 
make  diligent  search  above  all  for  such  complications  as  may  require 
surgical  interference.  It  may  be  advisable  in  such  conditions  to 
suspend  specific  treatment,  but  immediate  reinoculation,  perhaps  with 
an  increased  dosage,  may  be  more  likely  to  be  productive  of  good. 

(7)  Use  every  known  means  throughout  of  securing  toxic  elimination, 
of  sparing  the  heart  from  needless  strain,  and  of  tiding  it  over  the 
period  of  greatest  stress. 

Resume  of  results  obtained  by  various  observers  and  their  conclusions. — 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  I  I  5 

Although  I  have  always  been  one  who  thinks  that  far  too  much  regard 
can  be  made  in  medicine  to  statistics  which  may  be  inherently  falla- 
cious, yet  none  the  less  it  is  certain  that  every  form  of  treatment  will, 
be  judged  by  the  case  mortality  and  incidence  of  complications 
experienced  during  its  employment.  The  pathogenity  of  the  Pneumo- 
coccus  and  so  the  death-rate  varies  greatly  in  different  epidemics,  and 
such  factors  as  age  and  previous  habits  of  the  individual  are  well 
known  to  be  important  prognostic  points,  so  that  if  statistics  are  to 
have  any  value  an  adequate  number  of  truly  comparable  cases  treated 
upon  orthodox  lines  are  essential  to  serve  as  controls — this  unfor- 
tunately is  not  always  possible,  and  where  it  cannot  be  done  the 
assumption  must  be  made  that  the  death-rate  would  have  otherwise 
approximated  to  the  normal,  which  may  be  taken  as  between  16  and 
20  per  cent. 

Wolf  {Journal  of  Infectious  Diseases,  igo6^  p.  739)  treated  14  cases 
with  vaccines  during  an  epidemic  in  which  the  total  mortality  was 
40  per  cent. 

II  of  the  14  cases,  or  78*5  per  cent.,  recovered. 
3       .>       M         ,,         21-5         „  died. 

In  10  of  the  II  cases  which  recovered  the  crisis  occurred  within 
thirty-six  hours  of  the  first  inoculation. 

Leary  {Boston  Med.  and  Surg.  Journ.,  1909,  p.  714)  records  his 
results  in  83  cases.  Of  these,  34  were  alcoholics  in  whom  the  normal 
death-rate  was  50  per  cent.  Of  these  34  cases  only  5  died — a  mortality 
of  177  per  cent.  Of  the  other  49  cases  only  2  died— a  mortality  of  only 
4  per  centc     The  death-rate  among  the  whole  83  =  9*7  per  cent. 

Rapid  relief  of  toxasmic  conditions  was  noted,  and  in  cases  of 
otherwise  uncontrollable  delirium  the  abatement  thereof  was  prompt. 

Craig  {Medical  Record,  November  i8th,  1911)  records  his  results  in 
20  cases  among  old  sailors,  all  over  60,  most  much  older  (80-90  years 
old).  Most  were  alcoholics,  nearly  all  had  chronic  nephritis,  arterio- 
sclerosis and  dilated  hearts.  The  average  death-rate  in  the  institution 
for  the  preceding  five  years  from  pneumonia  had  been  65  per  cent. 
Yet  of  these  20  only  4  died,  a  death-rate  of  20  per  cent.,  and  of  these  4 
only  I  died  directly  from  the  pneumonia,  this  being  a  very  severe  case 
of  bilateral  disease  ;  of  the  other  3  cases  one  was  already  complicated  by 
purulent  pericarditis,  and  another  by  acute  uraemia  and  acute  dilatation 
of  the  heart. 

Charteris  {Glasgow  Med.  Journ.,  January,  1912,  p.  19)  obtained  much 
less  favourable  results  in  19  cases.  Ten  simultaneous  cases  which 
seemed  on  the  point  of  crisis  were  used  as  controls.  His  conclusions 
were  that  the  administration  of  a  stock  pneumococcal  vaccine  had  no 
marked  effect  upon  the  subsequent  course  of  the  disease,  the  mortality 


I  1 6  THE    BACTERIAL    DISEASES    OE    RESPIRATION. 

being  practically  identical — 20  per  cent,  in  the  two  series — that  the 
early  administration  of  vaccine  did  not  abort  the  disease  nor  prevent 
complications,  and  that  complications  were  relatively  frequent  in  the 
vaccine  series,  viz.  i  case  of  meningitis,  2  of  empyema,  and  i  of 
hyperpyrexia. 

It  is  very  easy  to  be  critical  and  perhaps  do  injustice  to  other  people, 
but  a  study  of  the  paper  leads  to  the  following  criticisms  :  (i)  That  the 
use  of  cases  obviously  about  to  crisis  as  controls  is  quite  inadmissible. 

(2)  That  of  the  four  cases  which  died  two  were  alcoholics  who  were 
delirious  or  aemi-conscious  when  treated. 

(3)  That  in  only  eight  of  the  nineteen  cases  was  a  dosage  of  10 
millions  of  a  stock  val;cine  exceeded  ;  in  eight  of  the  cases  it  was  under 
5  millions. 

(4)  That  in  two  of  those  that  died  an  initial  dosage  of  20  and  18 
millions  respectively  was  reduced  subsequently  to  10  and  2  millions 
respectively,  although  all  the  indications  that  can  be  gathered  from  the 
clinical  histories  were  for  maintaining  or  even  increasing  the  dosage. 

For  these  reasons  I  regard  his  conclusions  as  fallacious,  his  controls 
are  inadmissible,  and  all  that  the  paper  shows  is  that  the  administra- 
tion of  a  stock  vaccine  in  doses  already  well  known  to  be  inadequate 
failed  to  reduce  the  mortality  below  20  per  cent. 

Parry  Morgan  [Proc.  Roy.  Soc.  of  Med.,  vol.  iii.  No.  9,  Supplement, 
p.  165)  treated  43  cases  with  2  deaths — a  mortality  of  5  per 
cent.;  one  of  these  two  died  from  nephritis  after  the  pneumonia  had 
subsided.  Treatment  was  begun  at  periods  of  the  disease  from  the 
second  day  onward,  some  cases  being  treated  with  stock  vaccine,  some 
with  autogenous  ;  one  of  these  latter  cases  proved  to  be  a  streptococcal 
infection.  In  many  cases  he  repeated  doses  of  50  millions  of  auto- 
genous vaccine  and  never  saw  any  harm  result,  but  he  inclines  to  the 
view  that  a  dosage  of  15  to  30  millions  gives  the  best  result  in  the  average 
adult.  When  an  artificial  crisis  was  not  produced  the  temperature 
often  fell  by  lysis,  with  marked  improvement  in  the  symptoms.  For 
seven  of  the  most  interesting  cases  as  being  complicated  ones  and  the 
most  convincing  the  original  account  should  be  consulted. 

From  the  experience  gained  in  the  treatment  of  these  cases,  Morgan 
says  that  the  temperature  may  be  a  guide  but  often  is  not,  one  of  the 
most  noticeable  features  being  the  improvement  in  the  general  condi- 
tion without  much  change  in  the  temperature ;  the  anxiety  which  one 
often  feels  for  a  patient  is  relieved,  sleep  comes  readily,  the  appetite 
improves,  and  even  if  the  pulse-rate  does  not  fall  its  strength  is  well 
maintained.  At  other  times  there  is  a  fall  in  the  temperature  soon 
after  the  dose,  sometimes  even  in  a  couple  of  hours ;  if  this  is  the  case 
another  dose  is  indicated  when  the  temperature  rises  again. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  I  I J 

If  there  is  no  change  in  twenty-four  hours  the  dose  should  be 
repeated,  sometimes  being  increased,  but  more  often  decreased ; 
between  subsequent  doses  a  longer  interval  may  be  left.  For  various 
reasons  he  finds  the  opsonic  index  is  frequently  quite  unreliable  as  a 
guide  to  the  progress  of  immunity  in  pneumonia,  and  feels  that  some 
other  mjeasure  of  it  is  much  to  be  desired. 

Butler  Harris  {Brit.  Med.  Journ.,  June,  igog,  p.  1530,  and  Proc.  Roy. 
Soc.  of  Med.,  vol.  iii.  No  g,  Supplement,  p.  103)  considers  that— 

(i)   Successful  inoculation  for  pneumonia  is  possible. 

(2)  Inoculation  does  no  harm. 

(3)  A  vaccine  from  one  or  a  number  of  virulent  strains  should  be 
used. 

(4)  It  should  be  introduced  as  early  as  possible. 

(5)  The  estimation  of  the  opsonic  index  is  not  necessar}-. 

(6)  The  observation  of  the  temperature  and  physical  signs  is  a 
sufficient  guide  to  the  repetition  of  the  dose. 

(7")  Infections  of  the  lung  by  the  pneumococcus  which  fail  to  resolve 
after  an  acute  pneumonia,  as  well  as  pneumococcal  infections  of  other 
areas,  ought  certainly  to  be  treated  with  a  vaccine. 

He  found  that  a  dose  of  20  to  50  millions  might  be  given  without 
harm,  that  usually  a  fall  of  temperature  was  produced  in  a  few  hours. 
that  frequently  it  rose  again,  but  not  to  the  same  level,  and  that  it  was 
often  necessar}-  to  repeat  the  inoculation  once  or  twice.  He  is  con- 
vinced that  usually  a  distinct  reaction  in  favour  of  the  patient  is 
produced,  and  that  it  is  wise  to  begin  inoculations  before  the  nervous 
mechanism  suffers  much  inhibition.  In  the  sequelfe  of  pneumonia  he 
considers  the  use  of  a  pneumococcal  vaccine  as  sure  of  a  good  result 
as  that  of  a  staphvlococcal  one  in  case  of  boils. 

xA.fter  comparison  of  the  clinical  histories  of  his  cases  with  those  of 
Craig  and  of  Parry  Morgan  he  finds  that  the  effects  seen  b}-  each  of 
them  as  produced  by  bacterial  inoculations  in  cases  of  pneumonia  are 
practicallv  identical,  and  considers  that  every  case  of  pneumonia  should 
be  from  the  outset  regarded,  as  possibly  a  fatal  one,  and  suggests  that  a 
stock  vaccine  of  proved  immunising  power  should  always  be  employed 
as  earh'  as  possible  in  a  dose  not  exceeding  20  millions,  and  that  the 
preparation  of  the  autogenous  vaccine  should  be  at  once  proceeded  with. 
This  collective  evidence  is  surely  sufficient  to  warrant  the  unpreju- 
diced in  giving  a  fair  trial  to  vaccine  treatment  of  cases  of  pneumonia. 
What  he  is  entitled  to  expect  and   what  he   is    not   entitled   to   expect 
therefrom  has  been  fairly  laid  before  him.     It  only  remains  for  him  to 
pay  due  heed  to  the  various  considerations,  to  utilise  common-sense 
and  clinical  experience,  and  to  be  prepared  to  judge  results  with  due 
impartialitv. 


I  I  8  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

Unresolved  Pneumonia. 

As  we  have  seen,  the  leucocytes  are  held  to  be  the  chief  agent 
in  the  production  of  resolution  by  means  of  ferment  which  they 
liberate ;  hence  the  rational  procedure  in  a  case  of  unresolved 
pneumonia  would  seem  to  consist  in  the  promotion  of  a  leucocytosis, 
and  the  determination  of  a  leucocyte  flow  to  the  infected  area 
by  fomentations,  blisters  and  other  means.  Whether  it  has  been 
actually  observed  that  cases  of  acute  pneumonia  showing  a  relatively 
defective  leucocytosis  are  especially  apt  to  resolve  badly,  and  that  there 
is  a  leucopsenia,  relative  or  absolute,  present  after  failure  to  resolve,  I 
know  not ;  observations  upon  these  points  might  perchance  repay  the 
clinician  for  his  trouble.  Furthermore,  as  we  have  already  seen,  it  is 
hardly  reasonable  to  expect  that  the  administration  of  a  vaccine  will 
have  much  immediate  effect  during  the  stage  of  consolidation  in  an 
acute  attack.  For  these  two  reasons  it  would  seem  hardly  reasonable 
to  expect  that  a  vaccine  should  have  much  immediate  effect  upon  an 
unresolved  condition.  The-  blood  and  lymph  stasis  is,  however,  not 
then  so  complete  as  at  the  height  of  consolidation,  some  attempt  has 
been  made  at  the  re-establishment  of  the  circulation.  It  therefore 
follows  that  some  good  may  be  expected  to  accrue  from  a  course  of 
vaccine  treatment.     It  must,  however,  be  remembered — 

(i)  That  even  if  the  infection  were  an  unmixed  one  at  the  inception 
of  the  attack  it  is  hardly  likely  to  have  remained  so.  The  streptococcus 
or  M.  catarrhalis  will  almost  certainly  complicate  the  picture,  and  to 
these  attention  may  have  to  be  directed.  In  the  few  cases  which  I 
have  myself  investigated  a  mixed  infection  has  been  always  present,  and 
I  have  thought  it  the  better  practice  to  employ  a  mixed  vaccine. 

(2)  That  progress  necessarily  must  be  somewhat  slow. 

(3)  That  the  production  of  local  reactions  in  the  infected  tissues  is 
essential  to  cure,  and  that  such  dosages  must  be  used  as  will  produce 
this  effect.  A  50-million  dose  of  any  of  the  above  three  organisms  will 
do  to  begin  with,  but  should  stethoscopic  observations  and  clinical 
symptoms  show  failure  of  local  reaction  this  dosage  should  be  increased. 
Personally  I  have  found  ultimate  doses  of  500  milhons  essential  to 
complete  cure. 

Periodic  examinations  of  the  sputum  should  be  made  to  check  pro- 
gress and  eliminate  the  possibility  of  a  new  infection  having  been 
incurred,  and  to  ensure  the  continuance  of  treatment  until  the  pneu- 
mococcus  has  entirely  disappeared  from  the  sputum. 

In  one  very  interesting  case  of  mine  it  took  four  months'  treat- 
ment to  bring  about  a  satisfactory  clinical  condition,  and  an  additional 
eight  months  to  secure  the  desired  bacteriological  result. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  II Q 

Empyema,  Lung  Abscess,  etc. 

There  is  nothing  specially  to  mention  as  regards  the  vaccine 
treatment  of  these  conditions.  Treatment  will  be  guided  by  the 
considerations  which  govern  the  procedure  in  all  cases  of  abscess 
formation  and  of  sinuses  in  the  body  generally. 

Prevention,  as  always,  i%  better  than  cure,  and  that  a  considerable 
reduction  is  effected  in  the  incidence  of  these  .and  other  complications 
by  the  early  application  of  vaccine  treatment  to  all  cases  of  pneumonia 
is  agreed  on  by  all  who  have  had  mature  experience  of  this  procedure. 

In  the  case  of  lung  abscesses  especially  is  the  bacteriology  apt  to 
become  a  very  complicated  one  as  times  goes  on.  Streptococcus. 
M.  catarrhnlis,  B.  coli,  B.  proteiis,  B.  pyocyaneus,  B.  infiitenzcB,  M. 
tetragenus,  and  B.  of  Friedlander  are  a  few  of  the  acces5or\- 
microbes  which  may  make  their  appearance,  and  in  the  preparation 
and  use  of  the  autogenous  vaccines  considerable  discrimination  and 
care  may  be  required.  Free  drainage  is  a  sine  qua  non  to  cure  in 
cases  with  external  openings,  and  there  might  seem  to  be  reasonable 
grounds  for  the  fear  that  vaccine  treatment  might  bring  about  closure 
of  the  vent  or  sinus,  and  induce  local  accumulations  of  pus.  In 
practice  it  would  appear  that  this  danger  ma}'  be  easily  exaggerated. 
I  remember  one  patient  whom  I  was  treating  with  a  mixed  pneumo- 
coccus,  streptococcus,  B.  influenzcB  vaccine  for  chronic  antral  trouble, 
who  was  also  suffering  from  an  old  lung  abscess,  which  sometimes  dis- 
charged by  bronchus  as  well  as  through  a  persistent  external  sinus, 
expressing  great  anxiety  when  he  found  that  what  he  regarded  as  his 
safety  vent  was  closing  up.  I  reassured  him  and  treatment  was 
continued,  with  the  result  that  he  has  not  lost  a  day's  work  for  two 
years,  and  that  antrum  and  lung  abscess  have  caused  no  further  trouble. 
None  the  less  is  it  wise  whenever  possible  to  make  sure  that  any  sinus 
is  healing  from  the  bottom  by  occasional  probing  and  the  instillation  of 
citrated  salt  solution. 

Small  dosages  are  best  at  the  beginning  of  treatment,  but  as  time 
goes  on  they  should  be  increased  with  boldness  ;  a  slight  constitutional 
reaction  and  alteration  in  the  character  and  amount  of  discharge  are 
the  best  indications  of  adequate  dosage. 

Broncho-pneumonia  in  Children. 

This  condition  will,  I  venture  to  predict,  prove  one  of  the  most 
proiitable  of  all  fields  for  the  worker  in  vaccine  therapeutics.  Ignorance 
of  what  constitutes  the  defensive  mechanism  in  young  children  against 
bacterial  invasion  has  led  to  a  somewhat  natural  reluctance  to  apply 


I20  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

methods  applicable  to  the  adult.  The  results  achieved  in  the  treat- 
ment of  whooping-cough,  gonorrhceal  vuivo-vaginitis  and  conjunctivitis 
show  clearl}^,  however,  that  children,  and  even  infants,  do  respond 
readily  to  therapeutic  inoculation. 

In  broncho-pneumonia  we  have  a  disease  of  such  high  mortality  that 
ample  justification  exists  for  endeavours  to  find  some  specific  form  of 
treatment.  The  consolidated  areas  are  not,»as  a  rule,  so  large  that  any 
considerable  stasis  of  the  circulation  results,  as  in  the  case  of  lobar 
pneumonia,  and  upon  this  fact  additional  hope  of  success  maybe  based. 

Peculiar  difficulties,  however,  present  themselves.  The  bacteriology 
is  a  much  more  variable  one  than  in  the  case  of  lobar  pneumonia. 
Pneumococcus,  streptococcus,  B.influenzce,  B.  of  Friedlander  and  per- 
haps the  staphylococcus  and  other  organisms  may  be  responsible  for 
the  condition,  either  singly  or  in  any  combination.  If  vaccine  treat- 
ment is  to  be  resorted  to,  it  is  obvious  that  the  precise  nature  of  the 
infection  should  be  determined.  Unfortunately  children  are  very  apt 
to  swallow  sputum,  and  it  may  be  impossible  to  get  specimens  for 
examination ;  if  they  can  be  got,  then  all,  so  far,  is  well ;  if  they  can- 
not, lung  puncture  is  also  liable  to  prove  a  failure  owing  to  the  small 
size  of  the  consolidated  areas  ;  blood-cultures  might  prove  of  service, 
but  so  far  as  I  know  no  observations  have  been  made  in  this  direction. 
If  specimens  of  sputum  can  be  obtained,  the  best  procedure  would 
appear  to  be  to  make  examination  at  once  of  stained  smears,  and 
administer  stock  vaccine  of  proved  immunising  power  corresponding  to 
the  infection  found  while  the  autogenous  vaccine  is  in  course  of  pre- 
paration. If  no  specimens  are  obtainable  and  lung  puncture  and  blood- 
culture  fail,  then  I  think  it  will  be  more  than  justifiable  to  employ  a 
stock  vaccine  of  the  following  composition  :  In  each  c.c,  pneumococcus, 
10  millions;  streptococcus,  lo  millions;  B.  influenzce,  20  millions;  B.  of 
Friedlander,  20  millions  ;  the  dosage  to  be,  under  three  years,  2  minims ; 
three  to  five  years,  4  minims  ;  five  to  seven  years,  6  minims  ;  over  seven 
years,  8  minims,  the  indications  for  repeating  or  increasing  the  initial 
dosage  being  general  condition  in  the  first  place  and  temperature  in  the 
second.  As  a  general  rule  young  children  bear  relatively  high  dosages 
of  vaccine  extremely  well. 

Of  published  results  achieved  in  broncho-pneumonia  there  are  none 
as  yet  available,  but  one  or  two  private  communications  which  I  have 
received  are  very  favourable  to  this  therapy. 


CHAPTER    IX. 

VACCINES  IN  WHOOPING-COUGH,  DIPHTHERIA,  PYOR- 
RHCEA  ALVEOLARIS,  HAY-FEVER,  OZ^NA,  AND 
RHINOSCLEROMA. 

(a)  Whooping-cough. 

That  the  bacillus  of  Bordet-Gengou,  described  on  pp.  31  and  32, 
is  the  true  specific  cause  of  whooping-cough  is  now  generally  accepted, 
the  various  serum  reactions  affording  strong  confirmatory  evidence. 
Early  in  the  attack  the  Bordet  bacillus  appears  in  great  numbers  in 
the  secretions,  but  the  careful  investigations  of  Freeman  and  of  Martha 
Woolstein  into  the  bacteriology  of  this  disease  have  shown  that  even 
then  it  has  very  frequently  associated  with  it  the  B.  influenzcs,  and 
often  the  pneumococcus ;  the  great  liability  to  such  complications  as 
bronchitis  and  broncho-pneumonia  is  thus  explained  in  precisely  the 
same  way  as  the  liability  of  so-called  influenza  attacks  in  the  adult  to 
develop  into  acute  pneumonia. 

As  early  even  as  the  end  of  the  second  week  the  Bordet  bacillus 
has  almost  disappeared  from  the  secretions,  whereas  the  B.  influenziS 
and  pneumococcus,  and  perhaps  the  streptococcus  and  M.  catarrhalis. 
have  increased  considerably  in  numbers.  A  pure  infection  is  so  rare 
an  occurrence  that  the  symptoms  referable  to  the  Bordet  bacillus 
alone  may  be  almost  said  to  be  unknown.  The  bearing  of  this  upon 
the  vaccine  treatment  of  whooping-cough  will  be  dealt  with  present!}-. 
The  first  attempt  at  the  establishment  of  immunity  to  the  disease  was 
made  by  Bordet  about  ten  years  ago.  He  inoculated  twelve  healthy 
children  with  large  doses  of  a  vaccine;  very  soon  afterwards  they  came 
in  accidental  contact  with  a  case  of  whooping-cough,  with  the  result 
that  they  all  immediately  fell  victims  to  very  severe  attacks  of  the 
disease.  The  explanation  of  this  occurrence  is  now  taken  to  be  that 
contact  took  place  during  the  period  of  lowered  resistance  (or 
"  negative  phase  ")  consequent  upon  the  use  of  very  large  doses  of 
the  vaccine.  This  view  presented  itself  to  Freeman,  and  on  p.  97 
of  the  Proceedings  of  the  Royal  Society  of  Medicine,  vol.  iii,  No.  g,  supple- 


122 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


ment,  he  gives  a  detailed  account  of  the  many  careful  observations 
which  he  made  in  order  to  determine  the  correct  therapeutic  dose. 
Doses  varying  from  2  to  120  millions  were  employed,  the  final  con- 
clusion being  that  a  dosage  of  about  100  millions  gives  the  best 
results,  and  that  a  weekly  repetition  is  quite  safe.  By  these  means 
he  found  that  the  average  duration  of  the  disease  in  his  vacci- 
nated cases  was  reduced  to  4*3  weeks  as  compared  with  7*4  weeks 
in  those  who  received  inoculations  of  saline  solution  and  served 
as  controls.  It  must  be  remembered  that  many  of  these  cases 
were  treated  with  dosages  which  Freeman  now  recognises  to  be 
inadequate,  and  that  no  specific  treatment  was  directed  against  the 
complicating  organisms,  such  as  the  pneumococcus  and  B.  influenzce. 
This  he  now  advises  shall  be  done  as  a  matter  of  routine,  and  my  own 
limited  personal  experience  is  entirely  confirmatory  of  the  correctness 
of  this  procedure.  The  following  scheme  of  dosage  may  be  safely 
followed  : 

Age.  B.  Bordet. 

Under  i  year       ...         25 
1-2    years    .          .          .  .  50 

2-3        „       .  .  .  ;        100 

3-7        „       .  .  .  .        100 

Over  7  ,,       .  .         .       100 

Reinoculation  may  be  performed  at  intervals  of  five  to  seven  days, 
and  at  the  third  inoculation  a  double  dosage  may  be  employed  if 
thought  advisable. 

As  a  prophylactic  the  initial  dosage  corresponding  to  the  age  may 
be  doubled  in  seven  days  ;  and  this  again  doubled  if  thought  advisable 
after  another  seven  days. 

The  employment  of  the  above  combined  vaccine  for  this  purpose 
may  also  be  expected  to  diminish  the  liability  to  broncho-pneumonia, 
and  is  devoid  of  all  risk. 

As  to  the  duration  of  the  immunity  thereby  conferred  we  as  yet 
know  nothing  ;  probably  it  is  about  six  months,  so  that  two  series  of 
inoculations  yearly  may  suffice  to  confer  the  desired  protection. 

Saunders  and  collaborators  have  described  {Pediatrics,  March,  1912) 
their  results  in  forty  cases  of  w^hooping-cough  and  in  fourteen  children 
who  had  been  exposed  to  contagion.  They  also  began  with  small  doses, 
viz.  5  millions,  but  soon  concluded  that  the  dose  was  too  small  and 
increased  it  to  10-20  millions,  repeated  as  required.  Despite  the  fact 
that  this  increased  dosage  is  still  an  inadequate  one,  they  obtained 
results  which  led  them  to  the  following  conclusions  : 

(i)  That  as  a  prophylactic  the  vaccine  has  a  decided  value  ;  that 
whilst  it  is  true  that  vaccination  or  some  other  infection  will  postpone 


B.  influenzce. 

P 

neumococcus 

10 

2 

25 

5 

50 

5 

50 

10 

100 

10 

THE    BACTERIAL    DISEASES    OF    RESPIRATIOX.  1 23 

or  interrupt  the  course  of  pertussis,  vaccine  alone  will  absolutelv 
prevent  it.  The  immunity  is  of  uncertain  duration,  but  the  injections 
may  be  repeated  and  it  is  of  the  utmost  importance  to  postpone  the 
disease  until  the  child  has  passed  the  age  of  two.  The  failures  reported 
bv  some  observers  must  be  attributed  to  an  impotent  vaccine  or  to 
insufficient  dosage. 

(2)  That  as  a  remedial  agent  success  depends  upon  the  promptness 
of  administration  and  the  freedom  from  complications  at  the  time. 

(3)  In  no  case  should  other  treatment  be  withheld  if  indicated, 
especially  in  infants,  who  may  be  spared  convulsions  or  broncho-pneu- 
monia by  the  use  of  emetics,  sedatives,  or  some  aromatic  compound. 

(,4)  It  is  quite  possible  that  much  better  results  may  be  obtained  in 
late  cases  by  the  use  of  larger  doses  {and  the  combination  of  vaccme 
directed  against  the  allied  organisms). 

(5)  That  in  view  of  the  high  mortality  from  pertussis  in  3'oung 
children  there  should  be  a  systematic  effort  made  to  determine  the 
duration  of  artificial  immunity  and  to  keep  them  protected. 

(b)  Diphtheria. 

Diphtheria  from  the  point  of  view  of  the  vaccine  therapist  is  a 
disease  exhibiting  several  points  of  especial  interest,  and  it  is  therefore 
singularly  strange  that  so  little  attention  has  been  devoted  to  its  study 
in  this  direction. 

In  the  lirst  place  we  are  in  some  doubt  as  to  wherein  lies  the  defen- 
sive mechanism  of  the  body  against  the  B.  diphtherics.  AVright  has 
stated  that  there  is  no  opsonin  in  the  body  fluids  for  this  bactermm. 
Ruth  Tunnicliffe,  however,  finds  that  the  process  of  recover}-  runs 
parallel  to,  and  is  due  to  a  rise  in,  the  opsonic  index,  and  that  the  main 
factor  in  the  cure  of  the  disease  is  the  removal  of  the  bacilli  by  phago- 
cytosis and  consequent  cessation  of  the  absorption  of  toxin.  Antitoxin 
formation  seems  to  play  a  ver\'  subsidiary-  part,  for  recovery  is  often 
well  advanced  before  antitoxin  can  be  detected  in  the  blood — in  fact  it 
is  sometimes  apparently  absent  throughout.  Emery  {Immunity  and 
Specific  Therapy,  p,  409)  says  :  '•  The  observations  referred  to  previously 
show  clearly  that  the  process  of  cure  of  the  local  lesions  is  assisted  by 
the  production  of  an  opsonin.  And  there  is  every  reason  to  believe  that 
it  is  b}'  phagocytosis  that  the  bacilli  are  combated,  bacteriolysis  being 
very  doubtful  and  of  comparatively  small  importance.  The  cure  of  the 
disease  is  dependent,  therefore,  partly  on  antitoxin  formation  and  partly 
on  phagocytosis."  Against  this,  however,  is  the  fact  that  phagocytosis 
of  the  diphtheria  bacillus  is  very  rarely  seen  in  smear  preparations  made 
from  the  local  lesion. 


124  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

In  the  second  place  this  is  a  disease  in  which  conspicuous  success 
has  attended  the  use  of  antitoxin  serum  both  in  the  direction  of  dimin- 
ished mortahty  and  of  diminished  comphcations.  This  serum,  however, 
appears  to  be  solely  antitoxic  and  quite  devoid  of  anti-bacterial  properties. 
In  the  third  place  recent  investigations  are  showing  more  and  more 
clearly  how  important  are  so-called  "carriers,"  i.  e.  those  in  whom  the 
bacilli  persist  locally  after  the  subsidence  of  all  clinical  symptoms  in 
the  initiation  of  diphtheria  epidemics. 

The  statement  has  been  made  that  other  bacteria,  such  as  the  strep- 
tococcus and  staphylococcus  play  an  important  part  in  causing  the  dis- 
appearance of  the  B.  diphthericE  from  the  throat,  etc.,  after  an  acute  attack, 
and  the  proposal  has  emanated,  I  believe  from  Germany,  that  the 
process  may  be  hastened  by  spraying  the  infected  parts  with  living 
broth  cultures  of  the  Staphylococcus  aureiLS.  Good  results  have  been 
reported  by  one  or  two  observers,  but  I  cannot  but  feel  that  the  method 
is  fraught  with  danger  and  is  quite  unwarrantable. 

Walton  Smith  {Australian  Med..  Gaz.,  October  20th,  igio,  p.  543) 
gives  details  of  the  vaccine  treatment  in  the  case  of  a  girl  in  whose 
throat  the  B.  diphthericB  persisted  for  fifteen  weeks  after  antitoxin  was 
given,  recovery  being  otherwise  complete.  The  first  inoculation  with 
6  millions  B.  diphtheria  and  10  million  staphylococcus  (as  this  organism 
was  also  present)  resulted  within  twenty-four  hours  in  the  production 
of  a  well-marked  reaction  at  the  site  of  injection,  in  some  general  dis- 
turbance and  a  temperature  of  100*2°  F.  A  week  later  the  bacilli  were 
still  present,  so  an  inoculation  of  8  million  B.  diphtherice  was  given.  The 
reaction  was  ver}'  slight  on  this  occasion.  Subsequent  examinations 
of  the  throat  secretion  failed  to  show  the  presence  of  any  Klebs-Loeffler 
bacilli. 

The  suggestion  that  vaccine  treatment  might  be  combined  with 
antitoxin  seems  reasonable,  especially  in  cases  where  the  bacilli  tend  to 
persist,  and  there  is  some  ground  for  hoping  that  late  complications 
may  thereby  be  minimised.  It  must  be  left  to  future  observation  to 
decide  whether  further  combination  of  a  vaccine  of  the  predominant 
allied  organism,  streptococcus,  staphylococcus  or  M.  catarrhalis,  is  also 
advisable.  The  initial  dose  of  the  diphtheria  vaccine  should  not  exceed 
5  to  10  millions  for  the  present ;  future  observations  may,  however,  show 
that  higher  dosages  are  advisable  and  devoid  of  danger. 


(c)  Pyorrhoea  Alveolaris. 

A  very  great  amount  of  bacteriological  research  has  been  devoted  to 
this  disease,  and  numerous  reports  have  now  been  published  of  the 
results    of  vaccine   treatment.       These   are   almost   without    exception 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  1 25 

highly  favourable,  but  I  must  confess  to  considerable  scepticism.  In 
the  very  earliest  stages,  before  pus  pockets  are  definitely  formed,  strict 
attention  to  oral  hvgiene,  careful  local  treatment  by  a  thoroughly 
competent  dentist  who  has  time  to  devote  to  tedious  scaling  and 
polishing,  perhaps  combined  with  vaccine  treatment,  may  suffice  for 
cure ;  by  "  cure  "  I  mean  cure  beyond  recurrence,  provided  that  the  patient 
does  his  duty  for  the  rest  of  his  natural  life  and  pays  a  visit  ever}^  six 
months  to  a  competent  dentist.  But  when  the  condition  is  definitely 
established,  when  careful  pressure  around  the  gum  margins  results  in 
the  appearance  of  pus — sure  sign  that  there  are  pockets,  perhaps  an  eighth 
of  an  inch  deep  or  more — it  is  another  matter.  That  bacteria  are  resident 
in  the  tissues  of  the  gum  is  true,  and  that  vaccine  treatment  may  suffice 
to  eradicate  these  is  also  true,  but  not  all  the  vaccine  treatment  on  earth 
can  ever  influence  those  lying  in  the  space  between  the  tooth  and 
separated  tissue  of  the  gum.  Scaling  of  tartar,  polishing  the  teeth  so 
far  as  this  is  possible,  careful  brushing  night  and  morning  of  the  teeth 
with  a  moderately  hard  brush  and  an  acid  antiseptic  wash,  such  as 
"  albodent,"'  and  of  the  gums  with  a  softer  brush,  followed  by  massage 
with  the  finger-tip  and  eau-de-cologne,  will  all  help,  but  these  likewise 
will  not  suffice  to  re-establish  a  normal  condition  of  the  parts ;  and 
when  I  read  that  vaccine  treatment  combined  with  much  less  local  care 
than  this  suffices  to  tighten  loose  teeth  and  bring  about  elimination  of 
the  pus  pockets,  I  am  a  grave  doubter  of  the  writers'  powers  of  clinical 
observation.  But,  it  will  be  said,  is  there  no  cure  of  this  most  important 
disease,  a  disease  fraught  with  such  serious  immediate  and  remote 
dangers  to  the  patient's  health  ?  To  this  my  answ^er  is,  "  Certainly,  in 
a  considerable  percentage  of  cases,"  but  it  requires  a  skill  and  expendi- 
ture of  time  which  few  dentists  are  prepared  to  devote  to  it.  The  fault 
is  not  altogether  theirs  ;  the  public  are  as  much  or  more  to  blame,  and 
the  medical  profession  cannot  be  considered  to  be  exempt  from  responsi- 
bility. The  public  are  ignorant  of  the  consequences  of  the  disease,  and, 
being  ignorant,  are  ill-disposed  to  pay  adequately  for  its  cure.  They  go 
to  the  dentist  when  their  teeth  hurt  them,  and  are  prepared  to  have 
cavities  filled.  The  dentist  sees  or  fails  to  see  a  serious  condition  of 
pyorrhoea  ;  if  he  sees  it  he  often  fails  to  tell  the  patient  of  its  presence 
and  to  urge  its  treatment,  for  he  fears  to  lose  his  patient.  The  medical 
man  hardly  ever  knows  pyorrhoea  when  he  sees  it ;  it  is  a  disease  rarely 
described  in  the  text-books,  and  his  teachers  in  student  days  failed 
entirely  to  demonstrate  it  and  to  impress  its  far-reaching  consequences 
upon  him ;  if  they  did  they  would  only  stultify  themselves  in  the 
students'  eyes,  for  after  all  their  talk  they  would  perforce  have  to  leave 
the  condition  practically  in  statu  quo,  for  no  facilities  exist  at  general 
hospitals  for  its  adequate  treatment.     The  position  is  a  very  serious 


126  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

one,  but  it  is  not  easy  to  find  the  remed}- ;  perhaps  the  movement  for 
the  systematic  examination  and  treatment  of  school-children's  teeth  is 
the  best  that  is  available  ;  the  misfortune  is  that  the  condition  is  often 
established  even  at  this  early  age. 

As  such  measures  as  I  have  alread}'  mentioned  will  most  likely  fail 
to  secure  complete  cure  resort  obviously  must  be  made  to  other  means. 
Among  these  are  the  following  : 

(i)   Strictly  local  treatment  of  the  tissues  in  the  pockets. 

(2)  Attention  to  such  other  oral  conditions  as  follicular  tonsillitis 
and  post-nasal  catarrh. 

(3)  Perhaps  combined  with  these  the  use  of  appropriate  vaccines. 
Let .  us   consider    these    in    turn  :  by    (i)    I    mean    the    systematic 

removal  of  the  contents  of  the  pockets  and  the  topical  application  of 
such  medicaments  as  will  lead  to  the  removal  of  tissues  diseased  beyond 
repair,  to  the  stimulation  to  repair  of  such  tissues  as  are  capable  of 
repair,  to  the  obliteration  of  the  pockets  and  the  complete  re- 
approximation  of  tooth  and  gum.  There  are  limitations  to  success  by 
these  means,  the  chief  causes  of  failure  being  (i)  too  advanced  disease, 
in  which  case  extraction  is  the  only  remedy  ;  (2)  the  choice  of  unsuitable 
applications,  the  cause  of  failure  with  some  highly  skilled  and  con- 
scientious dentists ;  (3')  insufficient  perseverance  on  the  part  of  the 
operator  or  the  patient,  or  of  both. 

I  have  now  carefully  watched  for  several  years  patients  who  have 
been  methodically  treated  on  these  lines,  and  have  done  their  duty  b}' 
themselves  and  have  observed  a  completely  satisfactory  result  in  at 
least  60  per  cent,  of  the  cases  ;  when  recurrence  has  occurred  it  has 
been  slight  and  has  soon  yielded  to  a  further  short  course  of  treatment, 
which  is  perhaps  advisable  in  every  case  six  months  after  the  completion 
of  the  first. 

Let  us  now  consider  the  second  of  the  above  points.  Despite  all 
the  study  that  has  been  devoted  to  the  bacteriology  of  this  disease,  our 
knowledge  still  remains  in  an  unsatisfactory  state ;  the  reasons  for  this 
are  several,  among  which  may  be  mentioned : 

(a)  The  obsession  to  find  a  "  specific  "  microbe  for  every  disease. 

(6)  The  fact  that  far  too  little  attention  has  been  paid  to  the 
question  of  mixed  infection,  and  that  far  too  much  attention  has  been 
paid  to  the  results  of  cultural  observations  as  opposed  to  the  direct 
examination  of  stained  smears.  Many  organisms  associated  with 
pathogenic  conditions  of  the  mouth  are  exceedingly  difficult  to  grow, 
and  cultural  observations  may  prove  entirely  misleading. 

(c)  The  lack  of  regard  which  has  been  paid  to  many  organisms  as 
possible  causes  of  this  pathological  condition.  As  I  have  mentioned  in 
another  place,  cultures  of  mouth  spirochaites  and  spirilla  are  toxic  in 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  12/ 

the  extreme,  yet  little  regard  is  paid  to  them  as  factors  in  producing 
either  the  local  condition  or  the  general  constitutional  symptoms. 
Vincent's  organism  is  now  well  known  to  be  capable  of  setting  up  an 
acute  inflammatory  condition,  not  only  of  the  fauces  but  also  of  the 
tissues  of  the  limbs,  yet  little  importance  is  attached  to  this  organism, 
even  when  present  in  enormous  numbers  in  the  pus  of  a  pyorrhceic 
pocket. 

The  truth  about  the  bacteriology  of  this  condition  I  believe  to  be  as 
follows  :  It  corresponds  exacth'  to  that  of  other  conditions  about  the 
mouth  generallv,  and  closely  resembles,  even  if  it  is  not  actually 
identical  with,  that  of  follicular  tonsillitis  :  it  is  also  related  to  that  of 
post-nasal  catarrh,  but  less  intimately.  At  the  inception  any  one  of 
these  conditions  may  be  initiated  by  a  single  variety  of  micro-organism, 
the  pneumococcus,  Streptococcus  longus  or  hrevis,  staphylococcus 
{aureus  certainly,  albus  possibl}-),  and  perhaps  the  M.  catarrhalis. 
Secondary  invasion  by  other  organisms  soon  occurs,  combinations  of 
any  of  the  preceding  ma\-  be  established,  whilst  before  very  long  the 
spirochsetes,  spirilla,  vibrios  and  other  mouth  bacteria  also  gain  a  footing, 
and  may  even  in  course  of  time  completely  oust  the  original  invaders. 

As  these  conditions  are  similar  bacteriologically  the  absurdity  of 
endeavouring  to  treat  one  of  them  locally  and  of  neglecting  the  other  is 
at  once  obvious  ;  and  in  re-infection  from  another  focus  is  found  the 
explanation  for  many  of  the  relapses  which  occur  in  cases  of  pyorrhoea 
that  have  been  apparently  cured. 

We  are  now  in  a  better  position  to  consider  the  question  of  vaccine 
treatment.  Let  us  clearly  realise  that  it  is  illogical  and  unwise  in  the 
extreme  to  consent  to  any  shitting  of  responsibility.  The  dentist  has 
his  part,  in  my  opinion  the  more  important  part,  to  pla}- ;  the  vaccine 
therapist  cannot  fill  his  role  as  understud}' ;  if  the  dentist  in  attend- 
ance on  the  patient  is  not  able  or  willing  to  deal  with  the  infection 
locally  in  a  thoroughly  satisfactory  way,  then  the  ph3-sician  should 
allow  no  scruples  to  stand  in  the  way  of  advising  that  the  help  of  a 
more  able  or  more  willing  operator  should  be  sought.  Eight  out  of 
ever}^  ten  of  m\-  pyorrhceic  patients  I  have  found  to  require  no  more 
than  local  treatment. 

What  scope  is  there,  then,  in  this  condition  for  vaccine  treatment  ? 
Local  treatment  may  fail  to  effect  a  complete  cure  which  the  additional 
help  afforded  by  vaccine  treatment  may  secure  ;  in  other  instances 
cure  may  be  expedited  and  speed)'  relief  be  afforded  from  some  con- 
stitutional s\-mptoms.  and  arrest  be  brought  about  in  the  case  of  others. 
The  fairest  way  to  state  its  claims  to  consideration  is  that  it  will  rarelv 
fail  to  yield  some  definite  assistance  to  careful  methodical  local  treat- 
ment,   and  will   sometimes   succeed    in   brin^ins;'   about   verv  material 


128  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

improvement,  if  not  actual  cure,  in  cases  which  obstinately  refuse  to 
yield  to  local  treatment. 

/\s  I  have  said,  the  determination  of  the  true  bacteriology  is  no 
simple  matter  in  any  case.  It  will  not  by  any  means  suffice  to  express 
pus  from  various  pockets  and  culture  it  on  agar  or  blood-agar  and  in 
broth.  Special  media  may  assist  the  growth  of  certain  varieties  of 
organism  which  will  otherwise  refuse  to  grow,  but  a  conclusion  as  to 
the  relative  importance  of  the  various  bacteria  seen  in  films  and  grown 
in  cultures  is  best  made  only  after  a  week  or  more  of  careful  local 
treatment.  In  this  way  saprophytes  and  organisms  merely  resident  on 
the  surface  of  the  diseased  tissues  are  to  a  considerable  extent  elimi- 
nated ;  by  means  of  a  line  glass  capillary  pipette  a  little  secretion  is 
then  removed  from  the  bottom  of  several  pockets,  examined  directly  in 
smears  and  cultured  on  the  selected  media ;  a  little  scraping  from  the 
gum  lining  the  pockets  should  be  similarly  treated.  If  growth  be 
obtained  of  the  organisms  which  direct  examination  of  the  secretion 
and  infected  tissues  indicates  as  being  likely  to  be  concerned  in  the 
process,  vaccines  may  be  prepared  therefrom.  If  thought  desirable 
opsonic  index  determinations  may  be  made  towards  the  bacteria  which 
have  been  isolated ;  personally  I  don't  regard  it  as  worth  the  time  and 
money  expended  thereon.  Suitable  initial  doses  of  the  various  orga- 
nisms, perhaps,  are  streptococcus  5-10  millions,  pneumococcus  10 
millions,  staphylococcus  100  millions,  M.  catarrhalis  25  millions, 
streptothrix  10  millions,  the  interval  between  inoculations  being  live 
to  seven  days.  Treatment  may  have  to  be  continued  for  six  or  even 
twelve  months,  and  repeated  for  short  periods  at  intervals  to  guard 
against  relapse. 

Results  of  Vaccine  Treatment. 

A  few  abstracts  from  various  sources  will  serve  to  show  the 
divergent  views  taken  as  regards  the  aetiology  of  this  disease  and  the 
benefits  claimed  for  vaccines  in  its  treatment.  Williams  {Anier.  Journ. 
of  Med.  Sciences,  May,  1911,  p.  666)  has  reported  his  results  in  two 
small  series  of  cases.  The  organisms  which  he  held  to  be  accountable 
were  streptococcus,  pneumococcus,  M.  catarrhalis,  and  staphylococcus, 
singly  or  grouped.  Inasmuch  as  the  only  nutrient  medium  apparently 
employed  was  agar,  the  thoroughness  of  the  bacteriological  examination 
cannot  be  regarded  as  all  that  was  to  be  desired.  He  claims  that 
eight  cases  which  received  autogenous  vaccines  were  intractable 
cases  of  long  standing  which  had  received  careful  dental  treatment, 
while  twelve  other  cases  were  dispensary  ones  which  were  treated 
with    a  stock  vaccine    made    from    a  mixture    of  four   of  the    above 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  1 29 

autogenous  ones.  Reaction  to  an  inoculation  was  shown  within  one 
to  two  days  by  increase  of  sensitiveness  and  discomfort  of  the  teeth, 
and  once  by  sweUing  of  a  lymph-node  on  the  floor  of  the  mouth.  I 
append  short  details  of  the  cases  treated  with  the  autogenous  vaccines. 
Case  i. — Infection  streptococcal.  Four  years'  careful  intermittent 
dental  treatment  had  afforded  some  relief  of  symptoms,  but  this 
became  of  shorter  and  shorter  duration.  Eleven  inoculations  were 
given  in  thirteen  weeks ;  the  initial  dosage  was  10  millions,  the  final 
90  millions.  After  the  third  administration  the  patient  was  as  free 
from  symptoms  as  after  any  completed  course  of  dental  treatment. 
The  ultimate  result  was*  apparent  cure,  which  was  durable  twenty 
months  later. 

Case  2. — Duration  of  disease  about  five  years  :  Streptococcal  infec- 
tion. Two  years'  active  local  treatment  had  produced  great  improve- 
ment but  not  cure.  Two  years  after  discontinuing  local  treatment 
there  was  a  bad  relapse.  Three  doses  of  20,  30  and  40  millions  of 
stock  vaccine  brought  some  improvement  ;  local  treatment  was  then 
recommenced,  and  seven  doses  of  an  autogenous  vaccine  of  from  25-80 
millions  were  given  at  intervals  of  a  week.  Eighteen  months  later 
there  was  no  apparent  relapse. 

Case  3. — Streptococcal  infection.  Thirty  teeth  were  badly  involved 
and  the  general  condition  was  very  unsatisfactory.  Fourteen  inocula- 
tions of  an  autogenous  vaccine  were  given  in  fifteen  weeks,  at  the  end 
of  which  time  only  one  pocket  was  discharging,  the  others  being 
apparently  cured. 

Case  4. — Mixed  streptococcal  and  staphylococcal  infection.     Nine 

inoculations  were  given  in  seven  and  a  half  weeks,  the  dosage  of  the 
streptococcal  vaccine  being  increased  from  6-60  millions,  that  of  the 

staphylococcal  being  twice  these  amounts.     After  three  months  there 

was  no  relapse  from  an  apparent  cure. 

Case  5. — -A  very  severe  case  of  streptococcal  infection.     In  thirty 

weeks   eighteen    inoculations    were    given    in    dosages    of  from    10-50 

millions.      All  subjective  symptoms  disappeared   and  there  was  very 

great  improvement  of  the  pyorrhoea. 

Case  6. — Also  a  severe  case  of  streptococcal  infection.     Thirteen 

inoculations  of  from  7-50  millions  were  given.    Eight  months  after  the 

last  inoculation  slight  pus  was  found  in  one  pocket. 

Case  7. — Again  a  severe  streptococcal  infection.     Some  teeth  were 

so   loose  that  they  had   to    be  extracted.      Eighteen   inoculations  of 

6-90  millions  resulted  in  apparent  cure. 

Case  8  was  one  of  at  least  fifteen  years'  duration.    Two  inoculations 

of  12   and  16  millions    of  a  stock  streptococcal  vaccine  and  two  of 

autogenous  vaccine  were  given.    This  resulted  in  considerable  improve- 


130  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

ment.     Treatment  was  then  discontinued.    At  the  end  of  three  months 
the  improvement  was  maintained. 

Of  the  thirteen  cases  treated  with  stock  vaccine,  only  four  received 
more  than  six  inoculations.     Three  of  these  seemed  greatly  improved, 
and  a  favourable  opinion  was  formed  of  the  results  to  be  obtained  in 
this  class  of  case  from  the  use  of  a  stock  vaccine. 

MacWatters  {Proc.  Roy.  Soc.   Med.,  October,  1910,  supplement,  p. 
172)  relates  his  experience  of   forty-eight  cases,  of  which  thirty  had 
completed  treatment ;  this  consisted  in   removal  of  tartar,  the  use  of 
tooth-brush  and  carbolic  powder  before  each  meal,  and  a  mouth-wash 
of  4  per  cent,  sodium  chloride   and  0*5  per  cent,   sodium   citrate  to 
promote   osmosis.      No  local  applications    were  used.      Streptococcal 
vaccines,  autogenous  when  possible,  were  alone  used,  the  initial  dosage 
being    5  millions,  repeated  at  intervals  of  eight  days,  and  increased  to 
10  millions  as  the  lower  dosages  ceased  to  produce  a  reaction.     He 
states  that  the  effect  upon  such  constitutional  disturbances  as  dyspepsia 
morning    vomiting,   rheumatic    pains    and  depression  of    spirits    was 
very  marked. 

The  thirty  completed  cases  received  an  average  of  ten  inoculations  : 
of  these   twenty-one  showed  no  return  of  pus  two  months  after  the 
cessation  of  treatment,  while  the  other  nine  were  greatly  improved. 
The    obvious    comment    upon    these    results    is  that  a    lapse  of   two 
months   after   the    cessation    of  treatment    is    utterly    inadequate  for 
judgment  upon  the  question  of  cure :  complete   absence  of  symptoms 
after  six  months  will  point  to  the  probability  of  cure,  and  after  twelve 
months  may,  perhaps,  justify  the  application  of  this  term,  inasmuch  as 
it    must    remain    an    unsettled    point    whether   recurrence    after    this 
period   of  time    is  not  entirely  a  matter  of  re-infection  instead  of   a 
recrudescence  of  the  old  infection. 

Eyre  and  Payne  {Proc.  Roy.  Soc.   Med.,  December,  igog,   Odonto- 
logical  Section,  p.  2g),  carefully  studied  the  bacteriology  in  thirty-three 
advanced  cases  ;  inasmuch,  however,  as  they  began  these  investigations, 
which  were  to  guide  them  in  treatment,  with  the  preconceived  idea, 
based  on  the  animal  experiments  of   Washbourn  and  Goadby  with 
this  organism,  that  the  Streptococcus  brevis  is  a  harmless  saprophyte, 
which  it   most   certainly    is    not,  a  fallacy  was  introduced  into  their 
observations  from  the  very  beginning.     In  the  thirty-three  cases  they 
assigned  the  setiological  role  to  the  following  organisms  ; 

Staphylococcus  aiireus      ......       2  cases. 

M.  catarrhalis        ,.         .          .  .  .  .  .       g       ,, 

Streptococcus  pyogenes  longus  .         .         .         .       7       ,, 

M.  catarrhalis  a.nd  Streptococcus  pyogenes  longus      .     11       ,, 
Pneumococcus       .......       4      ,, 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  I  3  I 

The  Streptococcus  brevis  was  present  in  all  the  cases,  but  its  signifi- 
cance was  disregarded;  as,  however,  the  term  Streptococcus  pyogenes  longus 
was  applied  to  all  the  streptococci  which  were  pathogenic  for  animals 
some  of  their  group  may  include  forms  which  other  observers  would 
have  classified  as  "brevis.''' 

In  twenty-six  cases  which  were  selected  because  either  they  were  of 
great  severity  or  refused  to  yield  to  local  treatment  autogenous  vaccines 
were  employed  : 

In  2  cases  the  etiological  factor  was  held  to  be  Staphylococcus  aureus. 
„  6  „  „  „  „  „  M.  catarrhalis. 

„  6  „  „  „  „  „  Strept.  pyogenes  longus. 

,,  8  „  „  „  „  „  -V.      catarrhalis     and 

Strept.  longus. 
„  3  ..  ''  "  "  "  Pneumococcus. 

Before  beginning  vaccine  treatment  the  teeth  were  scaled  and  the 
pockets  packed  on  two  occasions  with  some  antiseptic,  such  as 
copper  sulphate,  tincture  of  iodine,  a  10  per  cent,  solution  of  formialde- 
hyde,  and  a  mildly  antiseptic  mouth-wash,  such  as  o"2  percent,  solution 
of  formaldehyde  or  hydrogen  peroxide  5-10  volumes.  The  doses  of 
the  various  vaccines  were — staphylococcal  50-250  millions,  M. 
catarrhalis  2"5-500  millions,  streptococcus  5-250  millions,  pneu- 
mococcus 5-100  millions,  their  later  experiences  leading  them 
to  employ  the  smaller  dosages.  Their  intervals  were  seven  to 
fourteen  days,  the  number  of  administrations  was  from  four  to 
twenty-five,  the  average  being  six  to  twelve,  and  treatment  was  con- 
tinued over  periods  ranging  from  one  to  nine  months.  "  Cure  *'  they 
regarded  as  being  established  when  the  teeth  were  firm,  the  mouth 
comfortable,  mastication  painless,  no  pus  could  be  expressed,  and  the 
muscular  and  arthritic  pains  and  digestive  disturbances  had  dis- 
appeared. 

They  state  that  rapid  improvement  was  noted  in  most  cases,  some 
being  more  resistant,  and  that  the  etiological  factor  is  of  some  impor- 
tance in  this  connection.  Infections  b}'  the  staphylococcus  respond 
most  quickly,  next  those  b}^  the  pneumococcus,  next  those  b}'  the 
streptococcus,  then  those  by  the  M.  catarrhalis,  the  most  refractory 
being  the  double  infections  by  the  streptococcus  and  3/.  catarrhalis. 

They  claim  to  have  examined  the  cases  after  considerable  intervals 
and  that  in — 

7  "  cure  "  still  persisted  after  12-15  months. 
12  ,,  „  g-i2 

2  ,,  „         under  g 

Four  were  improved,  i  had  died  from  malignant  disease. 

Three   of    the   cases    described    as    "  cured  "   were   shown    at    the 


132  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

meeting  before  which  the  paper  was  read,  and  the  consensus  of  opinion 
among  the  dentists  present  was  that  the  cases  were  not  "  cured,"  the 
condition  being  very  similar  to  what  might  have  been  anticipated  after 
local  treatment  only. 

Goadby  has  been  working  at  the  bacteriology  of  this  condition 
for  many  years  and  experience  has  compelled  him  frequently  to 
modify  his  views,  so  that  whereas  he  regarded  the  Streptococcus  brevis 
as  a  harmless  saprophyte  in  i8g6,  he  later  came  to  regard  it  as  the 
setiological  factor  in  a  considerable  percentage  of  cases.  To  a  variety 
of  the  streptococcus  which  he  prefers  to  call  a  strepto-bacillus,  but 
which  appears  to  be  almost  identical  with  the  Streptococcus  conglomeratus, 
so  commonly  present  in  the  mouth  and  especially  around  and  in  the 
tonsils,  he  now  assigns  the  chief  role.  For  the  results  which  he  has 
obtained  with  various  vaccines  the  original  articles  must  be  con- 
sulted {Proc.  Roy.  Soc.  Med.,  February,  igio,  Odontological  Section, 
p.  55  ;  Lancet,  1909,  vol.  i,  p.  663  ;  ibid.,  1909,  vol.  ii,  1875,  etc.). 

In  the  earliest  stages  he  considers  the  prognosis  to  be  60  per  cent, 
of  cures,  these  cases  apart  from  vaccine  treatment  being  regarded  as 
destined  not  only  to  advance  of  the  p37orrhoea  but  to  the  diseases  which 
have  been  shown  to  be  associated  with  that  condition. 

The  fallacy  in  this  conclusion  is  that  adequate  local  treatment  of 
the  disease  at  this  stage,  with  proper  supervision  of  the  mouth  at  six- 
monthly  intervals  and  the  inculcation  upon  the  patient  of  the  proper 
hygiene  of  the  mouth,  should  result  in  100  per  cent,  of  cures.  A  result 
of  60  per  cent,  of  cures  in  this  stage  is  synonymous  with  grave  deficiences 
on  the  part  of  both  dentist  and  patient. 

Carmalt  Jones,  from  the  ubiquity  of  the  Streptococcus  brevis  in  the 
lesions,  concludes  that  in  the  majority  of  cases  this  organism  is  the 
original  cause  of  the  condition,  infection  by  other  organisms  being 
frequently  superadded.  He  states  {Therapeutic  Inoculation,  p.  112) 
that  twenty  cases  of  simple  pyorrhoea  without  complications  have  been 
treated  at  St.  Mary's  Hospital  by  vaccines  of  the  Streptococcus  brevis 
in  doses  varying  from  10-50  millions,  the  usual  initial  dose  being 
20  millions.  The  results  of  treatment  lasting  from  one  to  two  months 
have  been  as  follows  :  cured,  six  cases  ;  much  better,  seven  cases  ;  better,, 
four  cases ;  unchanged,  three  cases.  Secondary  infections  by  the  M. 
catarrhalis  in  four  cases,  diphtheroid  bacillus  in  one  case  and  a  coliform 
bacillus  in  one  case  were  also  dealt  with.  Distinct  benefit  to  the  com- 
plications was  often  noticed. 

In  summarising  the  results  obtained  by  the  various  observers  we  find 
that  good  results  are  claimed  alike  by  those  who  attach  supreme 
setiological  significance  to  the  ubiquitous  Streptococcus  brevis  and  by 
those  who  entirely  disregard  its  claims  ;  assuming  for  the  sake  of  argu- 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  I  33 

ment  that  the  clinical  observations  of  all  are  equally  reliable,  the  only 
reasonable  conclusion  that  can  be  arrived  at  is  that  on  the  one  hand  we 
have  those  who,  in  the  majority  of  their  cases,  are  treating  the  primary 
infection  and  tend  to  neglect  any  secondary"  ones,  and  on  the  other 
hand  we  have  those  who  pay  exclusive  attention  to  secondary  or  mixed 
infections  and  disregard  the  primar}'  one.  Some  good  is  to  be  antici- 
pated from  either  procedure  and  appears  to  be  actually  obtained.  Of 
the  sum  total  of  good  achieved,  in  my  opinion  the  major  portion  is  to 
be  ascribed  to  the  limited  amount  of  local  treatment  which  is  also  given, 
and  to  the  fact  that  the  patient's  attention  is  more  clearh*  focussed  on 
the  existence  of  the  disease  and  on  the  ordinary  hygienic  measures 
which  promote  a  healthier  condition  of  the  mouth. 

A  clearer  conception  of  the  true  bacteriology  of  the  complaint  and 
of  the  prevalence  of  mixed  infection  would  broaden  the  view  that  should 
be  taken  of  the  applicability  of  vaccine  treatment  and  of  the  lines  along 
which  it  should  be  conducted. 

Conclusions. 

(i)  The  responsibility  for  the  treatment  of  pyorrhoea  alveolaris 
primarily  rests  with  the  dentist.  Despite  tlie  great  amount  of  attention 
which  has  been  paid  to  this  disease  in  recent  years  treatment  is  still 
frequently  inefficient.  Lack  of  thoroughness  and  of  persistence  and  the 
use  of  improper  local  applications  are  perhaps  the  commonest  cause  of 
failure  on  the  part  of  the  dentist. 

(2)  Vaccine  treatment  cannot  possibly  alone  suffice  for  cure  ;  it 
should  always  be  subordinated  to  careful  adequate  dental  treatment. 

(3)  That  it  should  be  resorted  to  when  the  latter  has  already  failed 
or  appears  to  be  likely  to  fail  to  effect  a  cure,  or  when  such  constitutional 
symptoms  as  chronic  articular  rheumatism,  muscle  pains,  gastro-intes- 
tinal  disturbances,  or  anaemia,  simple  or  pernicious,  require  urgent 
attention. 

(4)  When  the  pyorrhceic  condition  is  so  advanced  that  extraction  is 
the  only  course,  and  the  extraction  of  one  or  two  teeth  is  followed  by 
violent  constitutional  disturbances,  a  few  inoculations  with  the  appro- 
priate vaccine  may  greatly  assist  in  raising  the  patient's  resisting  powers 
to  the  absorbed  bacteria  and  their  toxins,  and  enable  the  dentist  to 
complete  the  extractions  with  less  danger  and  discomfort  to  the  patient. 

(5)  If  vaccine  treatment  is  to  prove  of  any  service  adequate  dosages 
must  be  emploj'ed  and  a  prolonged  course  may  be  necessary-.  The  signs 
of  adequate  dosage  are  the  production  of  a  definite  but  mild  reaction,  such 
as  any  of  the  following :  slight  malaise  within  eighteen  hours ;  increase  in 
local  or  general  symptoms,  as  tenderness  of  the  gums  or  teeth,  joint  or 
muscle  pains  ;    in  default  of  these  a  definite  improvement  in  the  local 


134  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

condition  showing  no  signs  of  relapse  after  five  to  six  daN's.  When  the 
appropriate  dosage  has  been  found  it  should  not  be  increased  so  long  as 
steady  progress  is  being  made  ;  when  this  ceases,  or  reactions  fail  any 
longer  to  be  produced,  then  increase  to  double  dosage  may  be  safely 
made. 

(6)  When  apparent  cure  has  been  brought  about  careful  re-examina- 
tion should  be  made  at  intervals  of  six  months.  In  the  event  of  relapse 
two  or  three  visits  to  the  dentist  should  be  insisted  on,  and  a  short 
course  of  vaccine  treatment  recommenced. 

(7)  In  those  patients  in  whom  constitutional  symptoms  are 
marked  two  or  three  inoculations  every  six  months  will  probably  assist 
in  the  maintenance  of  good  health. 

(8)  Owing  to  the  complexity  of  the  bacteriology  of  this  condition 
and  the  consequent  difficulty  in  preparing  the  appropriate  vaccine,  fail- 
ures in  its  vaccine  treatment  are  especially  apt  to  be  experienced  ;  in  such 
instances  the  vaccine  itself  should  come  under  suspicion  and  a  reinvesti- 
gation of  the  bacteriology  be  made.  The  flora  of  the  several  pockets  may 
vary  greatly  the  one  from  the  other,  so  that  it  is  not  sufficient  to 
examine  the  pus  from  one  or  two  foci  and  assume  that  a  similar  con- 
dition will  be  found  in  that  from  others.  A  member  of  the  streptococcus 
group  is  the  commonest  causal  organism,  but  it  is  not  the  only  one, 
and  mixed  infections  are  not  uncommon. 

(9)  Autogenous  vaccines  are  much  to  be  preferred  to  stock  ones. 
The  latter  should  only  be  used  when  insuperable  difficulties  stand  in 
the  way  of  the  preparation  of  the  autogenous. 

(d)  Hay -fever. 

In  this  distressing  complaint  we  have  a  condition  of  instability  of  the 
vaso-motor  centre,  and  a  great  susceptibility  of  the  mucous  membranes 
of  the  eyes  and  nose  especially  to  certain  influences,  the  result  being 
that  the  stimuli  applied  to  the  nerve-endings  in  the  nasal  mucosa 
upset  the  unstable  balance  of  the  vaso-motor  centre  ;  profuse  lacri- 
mation,  reddening  of  the  conjunctivse,  sneezing,  swelling  of  the  nasal 
mucosa,  excessive  formation  of  nasal,  tracheal  and  bronchial  mucus,  and 
perhaps  spasm  of  the  unstriped  muscle  of  the  bronchial  tubes  with 
resultant  asthma  are  thereby  set  up. 

The  stimuli  may  be  of  various  kinds,  such  as  certain  perfumes, 
either  of  flowers,  or  of  the  products  of  incomplete  combustion  of  petrol 
or  other  oils  ;  more  frequently  it  consists  of  a  toxin,  occasionally  of 
bacterial  origin  but  much  more  commonly,  as  Dunbar  has  shown, 
one  derived  from  the  pollen  of  various  flowers  and  grasses. 

Various  lines  of  treatment  may  be  therefore  followed,  such  as : 

(i)   Stabilising  the  vaso-motor  centre  by  cauterisation,  electrical  or 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  1 35 

chemical,  of  the  nerve-endings  in  the  nose.     This  method  has  yielded 
good  results  in  certain  hands. 

(2)  Removal  of  the  patient  from  the  reach  of  the  stimuli — a  course 
taken  with  many  who  leave  England  and  Germany  v/hen  the  pollen  is 
ripening,  and  depart  to  places  such  as  Heligoland  where  there  is  no 
pollen. 

(3)  Determination  of  the  toxin  to  which  the  patient  is  susceptible 
and  immunisation  against  it  either  by  means  of  serum  or  vaccine. 
Dunbar,  b}^  inoculating  horses  with  pollen,  produced  an  anti-serum, 
which,  while  yielding  good  results  in  some  cases  during  an  attack,  has, 
however,  not  proved  very  satisfactory  in  preventing  the  annual  recur- 
rence. Recourse  has,  therefore,  been  made  to  active  immunisation  by 
means  of  vaccine.  As  has  been  already  mentioned,  bacteria  or  their 
toxins  are  occasionally  able  to  produce  the  condition.  In  two  or  three 
instances  I  have  isolated  the  B.  septus  in  pure  culture  from  the  nasal 
mucosa  and  secured  complete  immunity  by  inoculations  with  250  and 
500  million  doses  of  the  autogenous  vaccine.  I  have  also  heard  of  one 
or  two  instances  where  the  use  of  my  combined  vaccine  for  colds  has 
produced  a  similar  result.  Carmalt  Jones  {Therapeutic  Inoculation,  p. 
126)  also  secured  considerable  improvement  in  one  patient  b}-"  the  use 
of  an  autogenous  vaccine  of  the  B.  aerogenes. 

Cases  such  as  these  wherein  a  bacterial  infection  is  the  active  agent 
must  form  a  very  small  percentage  of  the  total.  The  recent  researches 
of  Noon  afford  a  certain  method  of  determining  whether  susceptibility 
exists  to  pollen  toxin  ;  it  is  based  upon  the  well-known  ophthalmo- 
reaction first  applied  to  the  diagnosis  of  tuberculosis,  and  the  procedure 
is  as  follows  : 

One  gramme  of  the  pollen  of  Phleuni  pratense  is  extracted  with 
50  c.c.  of  water,  and  for  the  sake  of  convenience  the  extract  is  arbi- 
trarily assumed  to  contain  20,000  units  of  toxin  in  each  c.c.  The  follo\\'- 
ing  dilutions  are  prepared  from  the  extract  :  5000,  1500,  500,  150,  50,  15 
and  5  units  in  each  c.c,  this  wide  range  being  necessary  owang  to  the 
extreme  variation  exhibited  by  various  individuals  in  their  susceptibility 
to  the  toxin.  Two  or  three  drops  of  each  dilution  are  put  up  in  glass 
capillary  tubes  similar  to  those  employed  for  the  tuberculo-ophthalmic 
reaction.  The  test  is  applied  in  a  precisely  similar  way  ;  the  patient  sits 
with  head  thrown  back,  and  the  contents  of  a  capillary  tube  of  the  5-unit 
strength  are  instilled  into  the  conjunctival  sac  of  one  eye,  the  other 
serving  as  control.  After  two  or  three  minutes  the  eye  is  examined 
for  a  reaction  ;  the  first  sign  is  usually  a  tickling  at  the  inner  canthus, 
which  is  very  soon  followed  by  a  slight  but  distinct  reddening  of  the 
caruncle  ;  this  constitutes  a  "  slight  "  reaction.  If  the  congestion 
extends  to  the  adjacent  conjunctiva  it  is  called  "  marked,"  and  if  to  the 


136  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

whole  conjunctiva  it  is  regarded  as  "  very  marked."  If  no  reaction 
be  obtained  by  the  end  of  five  minutes,  the  next  stronger  dilution,  viz. 
the  15-unit  strength,  is  instilled  into  the  other  eye  and  developments 
awaited.  If  no  reaction  is  again  obtained  the  next  stronger  dilution  is 
employed,  reverting  to  the  eye  first  tested  and  so  on  until,  if  necessary, 
the  strongest  toxin  has  been  used.  If  there  is  still  no  reaction 
immunity  to  the  toxin  of  the  pollen  of  this  and  closely  allied  grasses 
may  be  considered  proved.  If,  however,  a  reaction  is  obtained  with 
any  of  the  dilutions,  then  susceptibility  has  been  demonstrated.  If  a 
"slight"  reaction  be  obtained  with  any  strength  then  a  "marked" 
reaction  will  be  obtained  with  a  triple  strength,  and  a  "  very  marked  " 
reaction  with  a  ten-fold  strength. 

Not  only  does  this  ophthalmo-test  serve  to  demonstrate  suscepti- 
bility, but  it  also  indicates  the  suitable  dosage  for  subcutaneous 
inoculation  with  a  view  to  the  production  of  immunity,  as  it  has  been 
observed  clinically  that  the  suitable  dose  for  the  latter  purpose  is  one 
third  of  a  cubic  centimetre  of  the  strength  which  yields  the  "  slight  " 
ophthalmo-reaction.  Thus,  if  the  latter  be  obtained  with  the  150-unit 
strength,  the  suitable  dose  for  inoculation  is  ^  c.c.  of  this  strength 
of  toxin  or  I  c.c.  of  the  50-unit  strength.  For  purely  protective  pur- 
poses this  dose  should  be  repeated  in  eight  to  ten  days.  After  a  similar 
interval  the  next  higher  dosage  may  be  employed,  and  so  on,  success- 
ful immunisation  being  shown  to  have  been  secured  by  failure  to 
respond  to  the  ophthalmo-test  with  the  5,000-unit  strength.  During 
the  hay-fever  season  it  is  well  to  begin  treatment  with  half  the  dosage 
as  above  determined,  the  same  rule  holding  in  the  event  of  the  patient 
seeking  relief  from  an  actual  attack  ;  in  this  event  not  only  should  the 
dosage  be  halved,  but  the  intervals  between  administrations  should  be 
likewise  reduced;  five  days  is  then  a  suitable  interval.  Just  as  the 
application  to  the  eye  of  two  or  three  drops  of  the  5000-unit  strength 
will  indicate  final  immunity,  so  the  failure  to  respond  to  the  applica- 
tion five  days  after  each  inoculation  of  two  or  three  drops  of  the 
strength  triple  that  used  for  the  last  inoculation  will  serve  to  indicate 
that  increased  dosage  is  then  advisable.  The  elaboration  of  this  highly 
scientific  method  of  treatment  is  of  such  recent  date  that  it  is  hardly 
as  yet  possible  to  dogmatise  about  results.  So  far  as  one  can  judge 
from  the  experience  of  the  past  season,  a  considerable  measure  of 
success  is  to  be  anticipated.  Many  patients  have  escaped  completely, 
and  the  greater  majority  have  suffered  from  nothing  but  very  mild 
attacks.  With  the  adoption  of  a  more  highly  polyvalent  vaccine  even 
better  results  may  be  secured. 

Ellern  {Dent.  nied.  Woch.,  No.  34,  1912)  records  an  interesting  series 
of  observations  made  during  the  past  season  in  Germany.     He  tested 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  1 37 

both  the  ophthalmo-reaction  and  the  therapeutic  effect  of  pollen  toxin 
prepared  at  St.  Mary's  Hospital  in  a  series  of  thirteen  cases.  He  found 
that  the  concentrations  required  for  obtaining  the  ophthalmo-reaction 
in  his  patients  reached  higher  levels  than  in  Freeman's  observations  ; 
being  that  of  50  units  only  in  the  most  susceptible  cases  ;  the  greater 
number  showed  subjective  symptoms  only  with  one  of  500  units  and 
distinct  objective  signs  only  with  the  1500  units  concentration.  Healthy 
individuals  were  not  affected  by  the  5000  unit  strength. 

As  to  the  relation  of  the  ophthalmo-reaction  to  the  therapeutic  dose, 
he  found  that,  at  least  during  the  period  of  prevalence  of  hav-fever, 
this  was  by  no  means  constant,  and  that  in  some  patients  who  felt  sub- 
jective improvement  in  their  symptoms  the  concentration  required  to 
produce  the  ocular  reaction  fell. 

For  therapeutic  purposes  he  began  with  a  dose  corresponding  to 
one  fifth  of  the  concentration  required  to  produce  the  ophthalmo-reac- 
tion and  repeated  it  at  intervals  of  five  days  :  higher  initial  dosage  he  does 
not  consider  desirable.  No  serious  symptoms  ever  appeared  as  the 
result  of  inoculation  and  there  was  no  rise  of  temperature ;  attacks  of 
typical  hay-fever  of  short  duration  occasionally  occurred  and  once  an 
asthmatic  attack  supervened.  Doughy  swelling  with  tension  and  pain 
at  the  site  of  inoculation  frequently  occurred,  but  these  symptoms  sub- 
sided in  from  one  to  two  days. 

The  number  of  injections  varied  from  4  to  g — only  few  received 
less  than  6  ;  the  dosage  from  25  to  125  units  as  an  initial  and  100  to  250 
units  (the  latter  in  nine  cases)  as  the  final  dosage. 

The  results  were  :  unchanged  2,  improved  5,  markedly  improved  6, 
as  compared  with  attacks  in  previous  years.  The  two  unimproved 
cases  gave  up  treatment  prematurely. 

Most  of  the  patients  declared  their  willingness  to  again  undergo  treat- 
ment next  year,  but  all  suffered  from  hay-fever  for  shorter  or  longer 
intervals.  Ellern  draws  attention  to  the  fact  that  in  Germany  hay-fever 
has  been  less  severe  this  year  than  last ;  for  instance,  he  made  inquiry 
of  twenty  cases  not  treated  specifically ;  their  experience  had  been,  4 
as  last  year,  14  less  severely  attacked,  and  2  very  much  less  severe  attacks. 
He  therefore  considers  that  the  difference  between  the  two  series  is  too 
small  to  enable  any  definite  conclusion  to  be  formed,  but  admits  that 
he  may  also  have  started  the  treatment  too  late  in  the  season. 

{e)  Ozcena  or  Atrophic  Rhinitis. 
Bacteriology. — Abel    made   a    bacteriological    examination    of    the 
atrophic  nasal  mucosa  in  100  cases  of  ozsena.  and  found  in  each  one  of 
them  a  bacillus  resembling,  but  not  identical  with,  the  bacillus  of  Fried- 
lander.     It  is  a  non-motile  capsulated  Gram-negative  bacillus  which 


138  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

forms  a  colourless  sticky  growth  on  agar,  which  is  so  moist  that  it 
slides  down  to  the  bottom  of  the  slope.  In  stab  cultures  it  spreads  out 
over  the  surface  of  the  agar  and  does  not  form  the  nail-head  growth 
characteristic  of  the  bacillus  of  Friedlander.  Its  growth  on  gelatine  is 
similar  to  that  on  agar  and  does  not  liquefy  the  medium. 

It  does  not  produce  indol  in  peptone  water. 

Its  fermentative  properties  are  much  less  active  than  those  of  the 
bacillus  of  Friedlander.  In  two  or  three  days  it  forms  slight  acid  in 
litmus-milk,  but  no  coagulum.  It  forms  acid  and  gas  in  mannite, 
dextrose,  maltose  and  raffinose  within  two  days,  in  adonite  and  dextrin 
within  three  days,  in  saccharose,  sorbite  and  lactose  within  four  or  five 
days,  but  not  in  dulcite  or  inulin  at  all.  When  this  organism  is  injected 
subcutaneously  into  mice  it  proves  fatal,  when  subcutaneously  into 
guinea-pigs  no  abscess  is  formed,  but  if  the  peritoneal  route  be  adopted 
death  is  brought  about  in  about  half  the  animals. 

Abel  found  this  organism  in  every  case  of  atrophic  rhinitis,  but 
never  in  any  other  diseased  condition  of  the  nose.  He  employed  it  to 
inoculate  a  healthy  human  nasal  mucosa  and  initiated  an  atrophic 
condition. 

Vaccine  treatment. — Page  {Jonrn.  Medical  Research,  July,  1912,  p.  489) 
found  this  organism  in  two  cases  of  ozaena  and  employed  vaccines  of  it 
in  them  for  therapeutical  parposes.  In  the  first  case  inoculations  were 
given  every  three  days  (no  dosage  is  indicated).  The  patient  noted 
continued  subjective  improvement,  there  was  diminished  crust-forma- 
tion and  increased  secretion  of  mucus.  After  three  months'  treatment 
the  improvement  under  this  form  of  treatment  alone  was  marked,  but 
inasmuch  as  the  right  frontal  sinus  was  involved  cure  had  not  then 
been  produced,  nor  was  this  to  be  anticipated.  The  second  case  was 
one  of  twenty-five  years'  standing.  In  addition  to  the  B.  ozcencB,  the  B 
pyocyaneus,  streptococcus  and  Staphylococcits  candidus  were  also  present 
A  mixed  vaccine  of  the  first  two  organisms  was  employed  ;  after  four 
inoculations  at  weekly  intervals  the  fcetor  was  diminished,  the  nose  and 
throat  not  so  dry,  and  the  discharge  was  moister  but  less  profuse.  The 
treatment  was  being  still  continued.  Cobb  and  Nagle  {Annals  of  Otology, 
Rhinology  and  Laryngology,  St.  Louis,  1912,  vol.  xxi)  have  also  found 
vaccine  treatment  of  distinct  value  in  cases  of  atrophic  rhinitis.  I  have 
myself  found  this  ozgena  bacillus  in  four  cases  of  early  atrophic  rhinitis 
and  employed  autogenous  vaccines,  combined  with  another  of  strepto- 
coccus, pneumococcus.  Staphylococcus  aureus  and  M.  catarrhalis  in  the 
respective  cases.  Initial  doses  of  fifty  millions  were  repeated  or  in- 
creased at  intervals  of  seven  days.  The  case  wherein  the  Staphylococcus 
aureus  was  also  present  made  very  slow  progress,  and  after  six  months' 
treatment  was  still  not  quite  cured.     The  other  three  cases  were  cured 


THE    BACTERIAL    DISEASES    OF    KESI'IRATION.  I  39 

after  about  this  interval ;  final  dosages  of  500  and  1000  million  organisms 
were  necessary  in  these  instances. 

(/)  Rhinoscleroma. 

Bacteriology. — Although  the  aetiology  of  this  distressing  complaint  is 
still  in  doubt,  there  seems  some  justification  for  regarding  it  as  a  bacil- 
lary  infection  due  probably  to  the  bacillus  of  Frisch  {vide  "  Zur  iEtio- 
logie  des  Rhinoscleroms,"  Wien.  med.  Wochenschr.,  1882,  Nr.  32,  and 
also  Kolle  and  Wassermann's  Handbuch  der  pathogenen  Mikro-organis- 
men,  1903,  Bd.  iii,  pp.  414-424).  This  organism  is  a  member  of  the 
bacillus  of  Friedlander  group,  but  differs  from  others  in  appearing  to 
be  actively  motile,  and  in  retaining  Gram's  stain  with  some  tenacity 
in  sections  of  tissues  hardened  with  Muller's  fluid.  Though  the 
majority  of  experimental  inoculations  on  animals  with  this  organism 
have  given  a  negative  result,  in  a  few  instances  typical  scleromas  have 
been  produced. 

Vaccine  treatment. — Guntzer  {Medical  Record,  July  24th,  1909,  p.  129) 
has  reported  on  two  cases  treated  with  vaccines  after  X-ray  and  other 
treatment  had  failed. 

In  the  first  case,  where  the  nose,  glottis  and  larynx  were  all  affected, 
he  gave  three  doses  of  250  millions  of  the  autogenous  vaccine  at 
intervals  of  four  and  eight  days  ;  the  last  two  of  these  injections  pro- 
duced marked  local  and  general  reactions,  bloody  discharge  from  the 
nose,  malaise,  headache,  and  rise  of  temperature.  Subsequently  doses 
of  375,  500  and  1000  millions  were  given  at  varying  intervals,  until  the 
patient  had  received  forty-three  inoculations.  At  the  end  of  this  time, 
although  cure  had  not  been  attained,  the  infiltrations  had  retrogressed, 
there  was  no  longer  dyspnoea  even  on  exertion,  and  the  patient  had 
been  able  to  resume  work.  A  year  later,  although  treatment  had  been 
discontinued  for  some  time,  the  improvement  had  not  only  been  well 
maintained,  but  had  been  even  continued. 

The  second  case  was  a  very  advanced  one,  the  general  condition 
was  bad,  there  was  nodular  deformity  of  the  nose,  the  anterior  nares 
were  almost  closed,  and  there  was  infiltration  of  the  upper  lip  ;  the 
tonsils  and  pillars  of  the  fauces  were  grown  together  into  a  compact 
mass  and  nearly  touched  on  opposite  sides ;  the  naso-pharynx  was 
almost  obliterated,  and  the  hard  palate,  but  not  the  larynx,  was 
involved.  The  vaccine  was  given  in  doses  of  250  to  1000  millions,  at 
intervals  of  three  to  seven  days,  until  thirty-two  injections  had  been 
given.  Local  reaction  was  marked  after  each  inoculation.  At  the  time 
of  the  report  the  disease  had  not  in  any  way  decreased,  but  it  had  like- 
wise not  advanced,  and  the  patient's  general  condition  was  very  much 
improved.      Treatment  was  to  be  continued. 


CHAPTER   X. 

THE    MIXED    INFECTIONS    OF   PULMONARY    TUBERCU- 
LOSIS  AND    VACCINES    IN    THEIR   TREATMENT. 

Out  of  the  chaos  into  which  the  specific  treatment  of  pulmonary 
tuberculosis  had  fallen  a  certain  amount  of  order  has  now  been  evolved, 
but  there  is  still  much  confusion  and  much  misapprehension,  and  this 
it  will  be  my  endeavour  to  remove  in  this  and  the  succeeding  chapter. 
Difficulties  have  been  created  by  the  too  ardent  disciples  of  the  various 
forms  of  treatment,  who  have  tried  to  reduce  man  to  a  mathematical 
formula,  and  haye  based  their  treatment  according  to  their  solution  of 
an  algebraical  problem.  They  have  failed  adequately  to  realise  that 
they  have  insufficiently  differentiated  the  signs  and  symptoms  due  to 
infection  by  the  tuberculosis  bacillus  from  those  due  to  infection  by 
allied  invaders ;  more  often  than  not  they  have  ascribed  to  one  invader 
what  should  have  been  attributed  to  another,  with  the  inevitable  result 
that  the  prescribed  form  of  treatment  has  been  misdirected  and  fore- 
doomed to  failure.  They  have  also  failed  sufficiently  to  realise  that 
the  human  being  is  a  very  highly  specialised  mdividual,  and  that  what 
applies  to  one  individual  may  fail  entirely  to  hold  with  regard  to 
another.  No  scheme  or  system  of  treatment  can  therefore  be  evolved 
which  will  suit  each  and  every  phthisical  person  ;  the  treatment  must 
be  moulded  to  the  individual,  not  the  individual  to  the  treatment. 

It  will  be  my  aim  in  this  chapter  to  consider  the  first  of  these 
points  in  some  detail,  and  to  endeavour  to  demonstrate  the  paramount 
importance  assumed  by  the  allied  or  secondary  invaders  in  many  cases 
of  pulmonary  tuberculosis,  and  to  indicate  the  means  whereby  this  may 
be  minimised  or  altogether  removed  and  the  case  brought  back  to  the 
much  simpler  form  of  an  uncomplicated  tuberculosis. 

In  the  succeeding  chapter  I  shall  endeavour  to  consider  how 
specific  therapy  can  best  be  utilised  in  this  simplified  condition  as  well 
as  in  that  of  pulmonary  tuberculosis  as  yet  uncomplicated  by  the 
advent  of  secondar}^  or  allied  invaders. 


THE    BACTERIAL    DISEASES    OF    RESPIRATIOX.  141 

The  Import  of  Mixed  Infection. 

The  term  •'•'mixed"'  infection  is  much  to  be  preferred  to  that  of 
"secondary"  infection  for  the  reason  that  certain  bacterial  diseases 
of  the  lung  predispose  to  subsequent  invasion  of  the  pulmonary  tissues 
by  the  B.  ttiherculosis,  the  latter  infection  being  then  the  secondary  one, 
the  former  the  true  primary  one.  In  other  instances  the  reverse 
holds  true,  to  a  primary  invasion  of  the  tissues  by  the  B.  tuberculosis 
secondary  invaders  become  superadded.  The  ultimate  result  may  be 
the  same,  but  in  the  earlier  stages  the  conditions  are  very  different,  and 
the  methods  of  treatment  may  require  to  be  verv  different.  In  the  earl\- 
stage  in  the  first  instance  the  problem  is  the  prevention  of  the  advent 
of  the  tubercle  bacillus  to  pulmonarv  tissues  which  are  in  a  condition 
called  by  French  physicians  '"' pras-tuberculous/'  and  to  remedv  this 
prse-tuberculous  state ;  in  the  latter  instance  the  problem  is  to  prevent 
the  advent  of  other  pathogenic  bacteria  to  pulmonary  tissues  already 
invaded  by  the  B .  tuberculosis  and  to  remedy  this  tuberculous  condition. 

In  the  later  stages  m  both  instances  we  have  to  deal  with  a 
co-existent  infection  by  the  B.  tuberculosis  and  other  pathos-enic 
bacteria. 

At  the  present  time  the  most  widely  divergent  views  are  held  as  to 
the  influence  which  other  bacterial  infections  of  the  lungs  exercise  both 
upon  the  initiation  of  the  tuberculous  process  and  upon  its  subsequent 
course.  Some  authorities,  basing  their  view  upon  the  verv  faUacious 
observations  that  many  of  the  organisms  isolated  from  tuberculous 
sputum  are  of  low  vitality  and  of  very  little  virulence  towards  animals. 
maintain  that  the  part  they  play  is  a  very  subsidiarv  one — in  the 
language  of  the  stage,  it  is  little  more  than  a  ■'■'  walking-on  '"  one.  Thev 
point  out  that  as  fever,  wasting,  caseation  and  softening  mav  all,  under 
certain  conditions,  be  produced  directly  b_v  the  tubercle  bacillus,  the 
symptoms  of  the  disease  should  in  all  cases  be  attributed  to  this 
bacillus,  and  to  it  alone. 

Other  authorities  would  attribute  a  preponderating  influence  to  the 
other  bacteria  in  the  production  of  the  advanced  processes  of  this 
disease  :  others,  again^  have  opinions  of  every  intermediate  grade 
between  the  two  extremes,  and  I  may  perhaps  be  permitted  to  make 
the  following  quotations  : 

Powell  and  Hartley  {Diseases  of  the  Lungs,  fifth  edition,  p.  402) 
write  as  follows  :  "  For  ourselves  we  cannot  but  believe  that  when  such 
micro-organisms  are  present  their  action  must  be  harmful,  and  that 
they  at  least  prepare  the  way  for  the  invasion  of  the  tissues  by  the 
tubercle  bacillus,  and  assist  in  that  suppurative  process  which  leads  to 
the  elimination  of  caseous  products  and  manifests  itself  clinicallv  bv 


142  THE    BACTERIAL    DISEASES    OF    RESPIRATION 

the  well-known  phenomena  of  hectic.  The  matter  requires  further 
investigation,  but  for  the  present  we  cannot  ignore  the  part  played  by 
secondary  micro-organisms  and  must  do  all  in  our  power  to  prevent 
their  gaining  access  to  the  patient." 

Sir  A.  E.  Wright  writes  :  "  While  the  suggestion  that  mixed  infec- 
tions must  be  expected  in  the  common  suppurative  processes  which 
occur  in  connection  with  surfaces  which  harbour  microbes  ma}^  well  be 
universally  acceptable  as  not  breaking  in  on  any  accepted  ideas^,  the  sug- 
gestion that  mixed  infection  must  therefore  be  considered  in  every  case 
of  phthisis,  lupus,  tubercular  caries,  tubercular  cystitis  and  tubercular 
ulceration,  in  the  very  nature  of  things  will  be  unacceptable  to  many 
clinicians.  Such  a  suggestion  will  be  felt  to  throw  doubt  not  only  on 
the  clearness  of  vision  of  those  who  have  sought  for  anti-tuberculous 
remedies  in  these  diseases,  but  also  on  the  critical  acumen  of  those, 
who,  without  taking  into  account  the  fallacies  which  are  incidental  to 
clinical  methods,  have  confidently  undertaken  to  pass  final  judgment  on 
anti-tuberculous  remedies  by  the  observation  of  their  clinical  effects  in 
cases  in  which,  in  addition  to  the  tubercle  bacillus,  other  pathogenetic 
microbes  may  have  been  at  work. 

"  Be  it  acceptable  or  unacceptable,  there  is  no  escape  from  the  fact 
that  practically  every  case  of  suppurating  lupus  is  complicated  by  a 
staphylococcus  infection  and  every  aggravated  case  of  lupus  with  a 
streptococcus  infection.  What  holds  true  of  lupus,  mutatis  mutandis 
is  true  of  every  tuberculous  affection  to  which  microbes  can  find 
access." 

Foulerton  [Transactions  of  the  British  Congress  on  Tfibercnlosis, 
London,  igo2,  vol.  iii,  p.  612)  points  out  that  "an  ox  may  have  the 
most  extensive  tuberculous  infection  of  the  pleural  or  peritoneal  sacs 
and  yet  will  frequently  be  in  absolutely  prime  condition  ;  there  is  no 
suggestion  of  disease  until  the  tuberculin  test  is  applied  or  the  animal 
is  slaughtered.  But,  given  a  breaking-down  of  tubercles  in  the  lung 
substance  with  secondary  infection  of  the  cavities  or  an  ulceration  of 
tuberculous  lesions  in  the  intestine,  and  one  finds  the  same  high 
temperature,  the  general  wasting,  and  the  same  active  destruction  of 
the  infected  tissue  which  characterise  the  average  case  of  chronic 
pulmonary  phthisis  in  man." 

Webb  {Tiiherculosis,  Klebs,  igog,  p.  5gg)  writes  as  follows :  "  It  is 
perhaps  a  fact  that  many  of  these  secondary  organisms  are  of  low 
vitality  and  non-virulent,  but  it  is  just  as  impossible  for  such  patients 
to  rid  themselves  of  these  as  of  local  infections,  such  as  acne  and 
furunculosis,  both  such  frequent  afflictions  of  the  tuberculous.  Sur- 
geons, familiar  with  bone  tuberculosis,  know  how  well  patients  with 
pure  tuberculous  disease  improve,  and  yet  how  intractable  are  those 


THE    BACTERIAL    DISEASES   OF    RESPIRATION.  1 43 

cases  with  mixed  infection.  Prudden's  well-known  experiments  on 
rabbits  show  conclusively  that  the  concurrent  action  of  two  distinct 
pathogenic  germs  may  result  in  a  considerable  modification  of  the 
lesions  which  either  could  produce  alone." 

The  question  of  mixed  infection  I  propose  to  discuss  according  to 
the  following  scheme  : 

(i)  Theoretical  consideration  of  the  question  as  to  how  far  con- 
comitant infection  may  be  truly  primary  or  truly  secondary. 

(2)  The  nature  of  the  bacteria  associated  with  the  B.  tuberculosis  in 
cases  of  pulmonary  phthisis. 

(3)  Method  of  determining  the  effect  of  the  toxins  of  other  bacteria 
upon  the  growth  of  the  tubercle  bacillus  in  vitro,  results  and  theoretical 
deductions. 

(4)  Method  of  determining  whether  deductions  from  observations 
in  vitro  hold  with  equal  force  in  the  living  subject,  and  the  application 
of  the  facts  so  learnt  to  the  prevention  and  cure  of  mixed  infections. 

Theoretical    Consideration    of   the    Question    as  to    how  far  Concomitant 
Infection  may  be  truly  Primary  or  truly  Secondary. 

The  determination  of  the  precise  period  of  life  at  which  invasion  of 
the  pulmonary  tissues  by  the  tubercle  bacillus  has  occurred  in  any 
given  person  is  a  \-ery  difficult  question.  That  infection  of  the 
glandular  system  occurs  in  a  very  high  percentage  of  children  in  the 
first  few  years  of  life  is  an  unquestioned  fact.  Some  authorities 
maintain  that  in  cities  it  is  of  almost  universal  occurrence.  Mac- 
Conkey  and  MacFadyen  actually  found  virulent  tubercle  bacilli 
present,  usually  in  the  mesenteric  glands,  of  about  25  per  cent,  of 
children  who  died  from  non-tuberculous  causes. 

The  assumption  that  the  pulmonary  phthisis,  which  makes  its 
appearance  in  considerably  later  years  of  life,  is  due  to  this  infection 
contracted  during  childhood  leads  to  many  difficulties,  such  as  that  of 
explaining  why  the  germs  should  lie  latent,  often  over  a  period  of 
many  years,  and  then  suddenly  take  on  active  growth.  Also  careful 
observations  have  tended  to  show  that  for  about  50  per  cent,  of  the 
cases  of  glandular  tuberculosis  in  children,  the  bovine  type  of  the 
tubercle  bacillus  is  responsible ;  whereas  in  pulmonary  phthisis  the 
bacillus  is  found  to  be  almost  invariabl}^  of  the  human  type.  It  thus 
follows  that  in  50  per  cent,  of  the  cases  a  metamorphosis  of  the  bacillus 
in  the  direction  of  change  of  type  must  have  occurred  ;  and  for  the 
possibility  of  this  occurrence  there  is  little  or  no  experimental 
evidence. 

Reinfection  by  the  human  type  bacillus  must  then  have  happened, 


144  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

and  what  is  true  for  50  per  cent,  of  the  cases  is  equally  likely  to  be 
true  for,  at  all  events,  a  considerable  proportion  of  the  other  50  per  cent. 

Naegeli  has  found  that  in  g6  per  cent,  of  autopsies  conducted  upon 
bodies  of  between  the  age  of  eighteen  and  thirty  years  evidence  of 
tuberculous  infection  was  present,  while  in  those  above  thirty  none 
were  found  free.  Infection  by  the  tubercle  bacillus  is  thus  a  practically 
universal  occurrence,  but  in  only  a  relatively  small  proportion  of  the 
cases  do  active  pulmonary  symptoms  supervene.  As  to  the  interval  of 
time  that  must  elapse  between  the  infection  of  the  pulmonary  tissues 
by  the  tubercle  bacillus  and  the  production  of  such  symptoms  as  enable 
the  detection  of  the  process  to  be  possible,  no  definite  limits  can  be 
fixed.  It  varies  much,  probably  with  each  individual,  and  may  be  a 
few  weeks  or  a  few  years.  The  determination^  therefore,  of  the  ques- 
tion whether  it  was  some  other  bacterial  infection  that  predisposed  the 
patient  to  infection  by  the  tubercle  bacillus  and  accelerated  the  process 
when  infection  had  occurred,  and  if  so,  precisely  what  was  its  nature, 
is  fraught  with  difficulty.  As,  however,  I  shall  produce  clear  evidence 
of  the  effect  of  concomitant  infection  upon  the  growth  of  the  tubercle 
bacillus,  it  is  only  reasonable  to  suppose  that  prior  manuring,  as  it 
were,  of  the  soil  will  conduce  to  subsequent  invasion  by  the  B.  tuher- 
culosis. 

Clinical  observations  have  shown  that  certain  bacterial  infections 
are  frequently  antecedent  to  the  outbreak  of  symptoms  of  pulmonary 
tuberculosis.  Thus  whooping-cough  and  measles  are  antecedent  to  a 
large  proportion  of  cases  of  tuberculosis  in  children  ;  it  is  frequently  to 
be  observed  that  glandular  enlargements  in  the  neck  are  preceded  b}' 
decayed  teeth,  a  condition  of  pyorrhoea  alveolaris,  eruptions  on  the 
scalp,  enlarged  tonsils  and  adenoids,  or  b}'  the  sores  set  up  by  chicken- 
pox,  and  that  unless  prompt  treatment  be  directed  against  these 
disorders  definite  tuberculosis  of  the  glands  may  ensue,  and  it  is  only 
logical  to  suppose  that  stimulation  of  the  tubercle  bacilli  at  other  foci, 
such  as  the  mediastinal  and  bronchial  glands  or  in  the  pulmonary 
tissues,  may  simultaneously  occur. 

Pneumonia  and  neglected  colds,  again,  enter  into  the  history  of  a 
large  proportion  of  cases  of  phthisis,  and  such  importance  do  some 
French  physicians  attach  to  bronchitic  and  asthmatic  conditions  as 
predisposing  causes  of  pulmonary  phthisis  that  they  are  wont  to  call 
them  prse-tuberculous  conditions. 

Whether  in  any  given  case  some  antecedent  bacterial  infection  has 
been  definitely  responsible  for  invasion  by  the  tubercle  bacillus  must, 
however,  rest  entirely  upon  pure  inference. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


145 


The   Nature  of  the  Bacteria  associated  with  the  B.  Tuberculosis  in  cases 

of  Pulmonary  Phthisis. 

I  have,  during  the  past  four  years,  carefully  and  minutely  examined 
the  sputum  of  fifty-two  cases  of  pulmonar}^  tuberculosis  with  a  view  to 
the  determination  of  the  nature  of  any  concomitant  infection,  with  the 
following  results  : 

Table  XIII. 

Total  Numher  of  Cases,  52. 

Streptococcus  . 

M.  catarrhalis    . 

Pneumococcus . 

B.  influenza 

M.  paratetragenns 

Staphylococcus  albus 

Staphylococcus  aiireus 

Diphtheroid  B. 

B.  of  Friedlander 

B.  proteus . 

B.  coli 

Only  exceptionally  was  the  mixed  infection  found  to  be  mon- 
organismal,  this  being  more  frequently  the  case  with  such  organisms  as 
the  staphylococcus,  B.  of  Friedlander,  or  B.  proteus,  than  with  those 
which  come  above  them  in  the  above  list ;  more  often  it  was  found  to 
be  binorganismal,  in  such  combinations  as  B.  influenza  and  pneumo- 
coccus, streptococcus  and  M.  catarrhalis,  pneumococcus  and  M.  catar- 
rhalis ;  and  still  more  frequently  the  combination  was  a  threefold  one, 
such  as  B.  influenzce,  pneumococcus  and  M.  catarrhalis;  pneumococcus, 
streptococcus  and  M.  catarrhalis. 

At  times  the  precise  character  of  the  mixed  infection  would  spon- 
taneously vary  from  time  to  time,  this  being  determined  to  a  certain 
extent  by  the  incidence  of  a  general  catarrhal  epidemic  among  the 
populace  ;  for  instance,. one  case  which  I  had  carefully  watched  and 
repeatedly  examined  during  two  years  without  ever  finding  any  con- 
comitant infection  other  than  that  by  the  Staphylococcus  albus,  suddenly 
contracted  a  superadded  infection  by  the  B.  influenzcE  and  pneumo- 
coccus, with  the  unfortunate  result  that  not  only  was  the  whole  of  the 
marked  progress  made  during  two  years  lost,  but  the  process  was 
transformed  from  a  fibroid  one  into  an  acutely  pneumonic  one,  and  in 
less  than  a  month  I  heard  of  the  patient's  death. 

10 


present  42 

times 

=  81 

per  cent 

41 

=  80 

19 

=  Z7 

„         12 

=  23 

,,        10 

,, 

=  20 

8 

=  15 

6 

=  12 

3 

=    6 

„         2 

=     4 

„          2 

=    4 

M          I 

)> 

=     2 

146  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

During  the  past  eight  years  I  have  had  exceptional  opportunities  of 
making  myself  acquainted  with  the  precise  nature  of  the  bacteria 
responsible  for  prevailing  catarrhal  epidemics,  and  v^hile  I  do  not  think 
that  phthisical  cases  are  more  disposed  to  catarrhal  infection  than  other 
people,  what  I  have  certainly  found  to  be  the  case  is  that  there  is  a 
greater  tendency  for  the  bacteria  to  invade  the  structures  in  the  chest 
instead  of  confining  their  activities  to  the  upper  respiratory  tract,  and 
that  they  cling  there  with  greater  pertinacity  when  once  they  have 
gained  a  hold.  It  thus  follows  that  one  or  two  examinations  of  the 
sputum  of  a  phthisical  case  by  no  means  suffice  to  determine  what  is 
the  nature  of  the  true  accessory  infection — by  that  I  mean  the  infecting 
organism  which  is  always  present  irrespective  of  the  fact  whether  a 
general  catarrhal  epidemic  may  be  in  progress  or  not ;  even  the  minute 
observations  which  I  have  bestowed  on  several  cases  have  not  sufficed 
to  enable  me  to  determine  what  was  the  true  primary  accessory  infec- 
tion. The  methods  which  I  have  elaborated,  however,  enable  us  to 
sort  out  the  bacteria  present  at  a  given  time,  and  say  which  are  exerting 
a  malignant  influence  and  which  apparently  are  not. 

It  is  due  to  causes  such  as  the  above  that  lists  by  various  observers, 
attempting  to  show  the  relative  frequency  with  which  the  various 
bacteria  occur  as  complicating  agents  in  cases  of  pulmonary  phthisis, 
show  such  considerable  variations. 

It  does  not  become  me  to  belittle  the  work  of  other  investigators, 
but  I  have  already  pointed  out  the  extreme  care  with  which  observa- 
tions upon  the  bacteriology  of  chest  infections  must  be  conducted  ;  in 
the  case  of  some  it  is  easy  to  determine  that  sufficient  care  has  not 
been  so  bestowed  ;  with  others  sufficient  details  to  estimate  the  probable 
accuracy  of  their  observations  are  not  available.  It  thus  becomes  a 
difficult,  nay,  an  impossible,  matter  to  collate  the  various  records  and 
draw  up  anything  like  an  accurate  table  to  display  the  relative  frequency 
with  which  the  various  bacteria  play  the  part  of  secondary  invaders  to 
the  B.  tuberculosis.  At  the  same  time  there  is  a  considerable  degree  of 
concordance  in  the  findings  as  regards  the  frequency  with  which  the 
streptococcus,  M.  catarrhalis,  pneumococcus  and  staphylococcus  are 
found  ;  for  instance,  this  is  the  exact  order  of  frequency  with  which 
they  were  found  by  Dr.  T.  W.  Hastings  (quoted  in  Kleb's  Tuherculosis, 
p.  591)  as  well  as  by  myself.  Other  observers  have  found  the  Staphy- 
lococcus {albus  or  aureus)  of  practically  universal  occurrence,  but  this  I 
feel  is  due  either  to  lack  of  care  in  excluding  contamination  from  the 
mouth  and  pharynx,  or  to  the  observations  having  been  conducted 
upon  cases  in  very  advanced  stages  of  the  disease,  for  although  I  cannot 
offer  figures  in  support  of  my  view,  I  yet  feel  strongly  that  the  earlier 
the  stage  of   the  disease,  the  less  the  likelihood  of  invasion  of  the 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  1 47 

tuberculous  foci  by  the  more  purely  pyogenic  bacteria,  and  the  greater 
the  probability  of  the  more  purely  catarrhal  organisms  complicating 
the  infection. 

The  results  of  post-mortem  examinations  such  as  are  recorded  by 
numerous  observers  I  think  should  be  altogether  excluded  from  con- 
sideration, for  it  is  impossible  to  exclude  agonal  and  post-mortem 
infection,  and  even  granting  that  such  had  not  occurred,  observations 
derived  from  so  far  advanced  cases  are  not  of  practical  application  to 
cases  in  the  early  stages,  and  these  are  those  with  which  we  are  the 
more  concerned. 

The  frequency  with  which  some  observers  have  found  the  B.  coli 
communis  I  am  altogether  unable  to  explain  ;  personally  I  have  only  once 
encountered  it  in  cases  of  pulmonary  phthisis  and  only  in  one  case  out 
of  several  of  lung  abscess,  that  particular  case  having  a  very  doubtful 
history  of  an  early  tuberculous  lesion  several  years  before  the  onset  of 
the  abscess  at  a  quite  different  place. 

In  cases  of  basal  phthisis  complication  of  the  infection  by  the  B.  coli 
would  be  more  likely  to  occur  than  when  the  tuberculous  process  is 
confined  to  the  upper  lobes. 

The  value  of  the  precise  determination  of  the  frequency  with  which 
the  various  bacteria  play  the  role  of  accessory  invaders  in  phthisis 
would,  as  I  have  already  hinted,  be  much  increased  if  more  regard 
were  also  paid  to  the  record  of  the  stages  of  the  disease  in  which  they 
are  found  ;  to  this,  personally,  I  intend  in  future  to  pay  more  heed, 
for  the  bearing  upon  the  question  of  prophylaxis  is  obviously  a  most 
important  one.  If,  as  I  believe,  the  catarrhal  organisms,  M.  catarrhalis, 
pneumococcus,  B.  influenzce,  M.  paratetragenus  and  some  varieties  (non- 
pyogenic  as  a  rule)  of  the  streptococcus,  show  a  far  greater  predilection 
for  earl}^  cases  than  do  the  more  purely  pyogenic  organisms  which 
appear  to  follow  in  their  tract,  measures  for  preserving,  not  only  early 
phthisical  cases,  but  also  those  who  merety  seem  to  be  predisposed  to 
pulmonary  phthisis,  from  catarrhal  attacks  assume  a  3'et  greater 
importance. 

Method  of  Determining  the  Ejfect  of  the  Toxins  of  other  Bacteria  upon 
the  Growth  of  the  Tubercle  Bacillus  ''in  vitro'' ;  Results  and  Theo- 
retical Deductions. 

During  my  investigations  into  the  bacteriology  of  the  catarrhal 
diseases  of  the  respiratory  tract,  I  have  been  frequently  struck  by  the 
observation  that  in  certain  cases  of  almost  pure  infection  by  the  B. 
infiuenzce  this  organism  refused  to  grow  on  the  culture  plates  unless, 
perchance,  development  also  occurred  of  a  few  colonies  of  such  organisms 


148  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

as  the  staphylococcus,  pneiimococcus,  or  M.  catarrhalis.  Luxuriant 
growth  of  the  B.  infitienscB  would  then  occur  in  immediate  proximity  to 
these  colonies,  but  not  elsewhere. 

It  occurred  to  me  to  study  this  symbiosis  further,  and  I  found  that 
it  sufficed  to  add  to  the  melted  blood  agar  2  or  3  c.c.  of  a  killed  broth 
culture  of  these  various  bacteria  prior  to  pouring  the  plates  and 
inseminating  them  with  the  B.  infltienzce.  By  this  device  I  have 
obtained  growths  of  this  organism  so  profuse  that  they  looked  more 
like  cultures  of  the  B.  coli  than  of  the  influenza  bacillus.  Previously 
I  had  recorded  in  the  Lancet  the  extraordinary  inhibitory  effect  that 
the  bacillus  of  Friedlander  exerted  upon  the  growth  of  other  micro- 
organisms in,  or  on,  the  same  medium. 

The  thought  then  suggested  itself — I  wonder  what  is  the  effect 
upon  the  growth  of  the  tubercle  bacillus  that  is  produced  by  the 
simultaneous  growth  of  the  other  such  bacteria  as  occur  in  secondary 
infections  of  pulmonary  phthisis,  or  by  their  toxins.  The  inability  to 
isolate  the  tubercle  bacilli  from  my  cases  was  at  first  an  obstacle  to 
the  solution  of  this  question,  but  this  fortunately  was  removed  by  the 
discovery  of  the  antiformin  method  of  securing  pure  cultures  of  the 
tubercle  bacillus. 

By  the  methods  already  outlined  I  proceeded  to  prepare  pure 
cultures  of  the  tubercle  bacillus  and  of  all  the  accessory  microbes  from 
several  of  my  cases.  Subcultures  of  the  accessory  microbes  were 
then  prepared  in  suitable  fluid  media — broth  for  staphylococci,  blood- 
broth  for  the  B.  influenzce  and  pneumococcus,  serum-broth  for  the  M. 
catarrhalis — and  these  allowed  to  incubate  at  37°  C.  until  such  time 
as  full  development  of  any  toxin  they  might  form  had  taken  place — 
usually  three  to  six  weeks — by  which  time  free  growth  of  the  tubercle 
bacillus   upon  the  Dorset's  egg  medium  had  also  occurred. 

Tubes  of  the  same  media  without  prior  insemination  with  any 
bacterium  were  also  placed  in  the  incubator  to  incubate  along  with  the 
other  tubes,  and  served  as  controls  in  the  way  which  will  be  indicated. 

The  fluid  cultures  were  then  sterilised  by  heating  for  one  hour 
at  a  temperature  of  6^°-yo°  C.  The  control  tubes  were  similarly  treated. 
A  sufficiency  of  large  tubes  of  Dorset's  egg  medium  was  then  prepared 
from  the  same  egg-mass  and  inspissated  and  sterilised  together,  so  that 
there  should  be  no  doubt  at  all  events  of  the  initial  precise  similarity 
of  the  soil  upon  which  future  growths  were  to  be  obtained.  Care  was 
taken  that  exactly  equal  amounts  of  medium  were  added  to  every  tube, 
and  that  the  angle  of  slope  in  the  inspissator  was  the  same  for  all ;  the 
tubes  being  the  same  size,  the  area  of  the  surface  of  the  medium  should 
be  the  same ;  if  measurement  showed  that  some  failed  in  this  direction 
they  were  not  utilised  for  the  purposes  of  these  experiments. 


PLATE    IX. 


Fig.  39". — No  toxin.     Five  weeks'  growth. 


Fig.  39.  —  Pneumococcal  toxin.     Five 
weeks'  growth. 


Fig.  40".  —  No  toxin.     P'ive  Fig.  40*. — Auto-pneumo-        Fig.  40''. — Auto-streptococcus 

weeks'  growth.  toxin.      Five  weeks'  growth.        toxin.    Five  weeks'  growth. 


PhotograpJis  by   D>-,  Ralph   Vincent. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  1 49 

That  number  of  tubes  of  the  finished  medium  which  corresponded 
to  the  number  of  cultures  of  the  accessory  microbes  plus  the  same 
number  to  act  as  controls  were  taken  and  all  water  of  condensation 
pipetted  off  from  them.     They  were  then  treated  as  follows  ; 

To  tube  T'  2  c.c.  of  the  sterile  toxin,  say  of  the  pneumococcus, 
was  added ; 

To  tube  V  2  c.c.  of  the  fluid  from  the  control  tube  correspond- 
ing to  the  pneumococcal  one  ; 

To  tube  IT'  2  c.c.  of  the  sterile  toxin,  say  of  the  B.  infltienzcs ; 
To  tube  ir^  2  c.c.  of  the  fluid  from  the  control  tube  correspond- 
ing to  the  B.  influenzcB  one  ; 
and  so  on,  the  (")  tubes  alwa3's  serving  as  controls. 

These  various  tubes  were  then  lightly  plugged  and  sloped  so  that 
the  added  fluid  bathed  the  whole  surface  of  the  egg  medium  ;  they  were 
set  aside  in  the  incubator  at  37°  C,  until  such. time  as  the  surface  of  the 
medium  was  moist,  but  nothing  more.  This  occupied  two  or  three 
days.  From  the  growth  of  the  tubercle  bacillus,  which  had  been 
isolated  from  that  same  case,  an  emulsion  in  i  per  cent,  salt  solution 
was  then  prepared  and  centrifugalised  at  very  high  speed  for  several 
minutes  ;  the  upper  portion  was  pipetted  off  and  examined  for  the 
presence  of  any  clumps ;  if  these  were  present  further  centrifugali- 
sation  was  performed  until  a  thin,  perfectly  uniform  emulsion  had  been 
ensured.  By  means  of  a  very  fine  sterile  glass  capillary  pipette  exactly 
equal  volumes  of  the  emulsion  of  tubercle  bacilli  were  added  to  each  of 
the  above  egg-medium  tubes  and  very  carefully  distributed  over  the 
surface  of  each.  The  tubes  were  then  sloped  and  placed  in  the  incu- 
bator for  forty-eight  hours,  when  they  were  re-plugged  with  dry  sterile 
woollen  plugs,  covered  with  a  rubber  cap,  returned  to  the  incubator  in 
an  upright  position  and  allowed  to  incubate.  At  the  end  of  three  to 
five  weeks  the  appearances  of  the  various  tubes  were  found  in  certain 
instances  to  differ  in  the  most  striking  way. 

Some  of  the  results  are  shown  in  figs.  39 — 42,  Plates  IX  and  X, 
For  instance,  figs.  39"  and  39'',  Case  (i),  show  the  different  growths 
obtained  after  five  weeks'  incubation  upon  two  tubes  of  Dorset's  egg 
medium,  the  former  having  been  manured  with  2  c.c.  of  blood  broth, 
•  the  latter  with  2  c.c.  of  blood  broth  in  which  a  pneumococcus,  isolated 
from  the  same  case  as  that  from  which  the  tubercle  bacillus  had  been 
derived,  had  been  allowed  to  elaborate  its  toxin.  The  acceleration  in 
rate  of  growth  of  the  tubercle  bacillus  produced  by  the  pneumococcal 
toxin  must  roughly  be  million-fold.  The  specimen  of  sputum  was  sent 
to  me  by  Dr.  Roemisch,  of  the  Wald  Sanatorium,  Arosa ;  it  came,  I 
believe,  from  a  rather  early  and  subacute  case  which  was  not  doing 
well. 


150  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

Figs.  40%  40^  and  40'^^  (Case  2)  illustrate  the  results  obtained  from  a 
case  in  which  the  left  upper  lobe  was  little  more  than  a  mere  shell 
surrounding  a  huge  cavity,  the  left  lower  lobe  being  in  a  condition  of 
almost  complete  consolidation  ;  there  was  a  very  doubtful  focus  of 
infection  at  the  right  apex ;  a  chain  of  enlarged  glands  ran  down  the 
right  side  of  the  neck.  Dr.  Rufenacht  Walters  kindly  confirmed  my 
clinical  observations.  Two  organisms,  a  pneumococcus  and  a  Strepto- 
coccus long'us,  were  isolated  from  the  sputum.  The  effect  their  respec- 
tive toxins  produced  upon  the  growth  of  the  concomitant  B.  tuberculosis 
is  well  seen  in  the  preparations  ;  it  will  be  noticed  that  the  acceleration 
produced  by  the  toxin  of  the  Streptococcus  longus  was  greater  than  that 
produced  by  the  toxin  of  the  pneumococcus. 

Figs.  41**  and  41^^  (Case  3)  illustrate  what  occurred  in  the  instance 
of  a  case  of  chronic  phthisis.  The  only  accessory  microbe  seen  in 
smears  and  isolated  in  cultures  was  a  peculiar  diphtheroid,  not  Bacillus 
septus.  It  will  be  noticed  that  the  growth  in  the  manured  tube  was  in 
no  respect  better  than  that  in  the  unmanured  one  ;  and  it  may  there- 
fore be  deduced  that  if  this  diphtheroid  organism  did  elaborate  a  toxin, 
this  latter  was  without  influence  on  the  rate  of  growth  of  the  allied 
B.  tuberculosis. 

Case  4,  illustrated  by  means  of  figs.  42'',  42''  42^  and  42^^,  was  one 
of  very  chronic  and  slowly  progressive  tuberculosis  of  both  apices,  and 
of  advanced  but  very  slowly  progressive  laryngeal  phthisis.  Repeated 
examinations  extended  over  a  period  of  two  years  failed  to  reveal  the 
presence  of  any  accessory  microbe  other  than  the  Staphylococcus 
albus. 

Figs  42''  and  42''  show  the  respective  growths  obtained  after  eight 
weeks'  incubation  upon  an  unmanured  soil  in  the  first  tube  and  upon 
one  manured  with  the  Staphylococcus  albus  toxin  in  the  second  ;  they 
will  be  seen  to  be  practically  identical.  These  observations  were 
repeated  several  times,  always  with  the  same  result  ;  if  anything, 
there  was  a  shade  better  growth  upon  the  unmanured  medium  than  upon 
the  manured  one.     The  significance  of  this  will  be  considered  later. 

Other  experiments  equally  clearly  showed  that  the  toxins  of  certain 
bacteria  had  a  very  marked  influence  upon  the  rate  of  growth  in 
artificial  cultures  of  the  tubercle  bacillus  associated  with  them  in  any 
given  case  of  phthisis.  It  therefore  remained  to  ascertain  whether  in 
those  cases  in  which  no  such  accelerating  effect  was  evidenced  the 
failure  was  due — 

(i)  To  an  inabihty  on  the  part  of  that  particular  strain  of  tubercle 
bacillus  to  respond  to  the  stimulus  of  the  toxin,  i.  e,  whether  the  fault 
lay  with  the  B.  tuberculosis. 

(2)  To  an  inability  on  the  part  of  that  particular  toxin  to  stimulate 


PLATE    X. 


Fig.  41  . — Auto-bacillary 

Fig.  41".— No  toxin.    Five         toxin.    Five  weeks' growth.         Fig.  42".— No  toxin.     Six 

weeks'  growth.  weeks'  growth. 


Fig.  42'. — Anto-.staphylo-  '^^^^'  Fig.   42''. — Hetero-strepto- 

coccustoxia.   Six  weeks'        Fig.   42'. —  Hecero-pneumo-        toxin.    Six  weeks'  growth. 
growth.  toxin.    Six  weeks'  growth. 


Photographs  hy  Dt.    Ralph    I'lnceni. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  I  5  I 

the  growth  of  the  tubercle  bacillus,  i.  e.  whether  the  fault  lay  with  the 
toxin. 

If  the  former  of  these  hypotheses  were  the  correct  one,  then  it 
should  not  be  possible  to  stimulate  the  growth  of  that  particular 
B.  tuberculosis  by  manuring  the  soil  with  any  other  toxins  of  proved 
powers  of  stimulation  derived  from  allied  organisms  in  other  cases  of 
tuberculosis.  Accordingly  some  of  the  pneumococcal  toxin  from 
Case  I  (above)  and  some  streptococcal  toxin  from  Case  II  (above) 
were  employed  to  manure  the  soil  of  two  culture-tubes.  These  experi- 
ments were  conducted  side  by  side  with  those  already  detailed  as 
42^  and  42'',  the  same  control,  42%  sufficing  ;  here  also  no  acceleration 
in  the  rate  of  growth  of  this  strain  (IV)  of  the  B.  tuberculosis  was 
produced,  cf.  figs.  42%  42%  42'^  and  inasmuch  as  repetition  on  several 
occasions  with  other  toxins  produced  the  same  result,  the  deduction 
appeared  to  be  justified  that  this  particular  strain  of  the  B.  tuberculosis 
was  incapable  of  stimulation  in  this  manner,  at  all  events  by  one  strepto- 
coccal, one  influenzal,  two  pneumococcal  and  one  staphylococcal  toxin. 

If  the  latter  hypothesis  were  correct  then  the  staphylococcal  toxin 
should  prove  incapable  of  stimulating  the  rate  of  growth  of  strains  of 
the  B.  tuberculosis  derived  from  other  sources.  Experiment  showed 
clearl}^,  however,  that  it  did  possess  this  power  towards  an  alien  strain 
of  the  B.  tuberculosis,  and  justified  the  conclusion  that  in  this  particular 
strain  of  the  B.  tuberculosis,  there  was  an  inherent  lack  of  power  to 
respond  by  increased  rate  of  growth  to  the  stimulus  afforded  by  the 
perfectly  efficient  toxin  liberated  by  the  concomitant  invader,  and  also 
to  that  afforded  by  such  other  active  toxins  as  were  investigated. 

From  these  experiments  it  follows  : 

(i)  That  there  are  certain  strains  of  tubercle  bacilli,  whose  rate  of 
growth,  in  vitro,  can  be  accelerated  by  the  aid  of  the  toxins  of  a  con- 
comitant invader. 

(2)  That  there  are  certain  strains  which  cannot  be  so  acted  on  by 
toxins  derived  either  from  a  concomitant  invader  or  from  a  heterologous 
source. 

(3)  That  there  are  toxins  elaborated  by  certain  strains  of  bacteria 
which  have  the  power  of  accelerating  the  rate  of  growth  of  the  tubercle 
bacillus  obtained  from  a  concomitant  infection. 

(4)  That  there  are  toxins  which  fail  to  exercise  this  power  upon  the 
tubercle  bacilli  derived  from  the  same  source,  and  yet  are  perfectly 
efficient  towards  other  strains  of  the  B.  tttberculosis. 

It  remained  to  investigate  the  following  questions  : 
{a)  Are  the  strains  of  tubercle  bacillus  falling  under  (i)  above  like- 
wise capable  of  stimulation  by  the  toxins  of  heterologous  bacteria,  and 
if  so,  of  what  bacteria  ? 


152  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

{b)   Do  the  toxins  which  possess  the  power  described  under  (3)  also 
influence  ahen  strains  of  the  tubercle  bacillus  in  a  similar  way  ? 

(c)  Are  there  toxins  (if  such  be  formed  b}'  the  bacilli)  which  fail 
to  stimulate  both  the  allied  B.  tuberculosis  a.nd  alien  strains  as  well. 

(d)  Will  the  filtered  products  of  bacterial  growth  act  in  the  same 
way  as  the  killed  suspensions  of  the  bacteria  in  their  culture  media. 

To  question  {a)  numerous  experiments  enable  , me  to  reply  that  a 
strain  of  tubercle  bacillus  capable  of  stimulation  by  the  toxins  of 
associated  bacteria  is  also  capable  of  stimulation  by  the  toxins  of 
bacteria  isolated  from  other  cases  of  pulmonary  phthisis,  the  degree 
of  stimulation  given  varying,  however,  with  different  organisms  and 
with  different  strains  of  the  same  organism  :  with  some  the  acceleration 
of  growth  is  very  great,  with  others  it  is  very  slight.  Roughly,  the 
bacteria  may  be  arranged  as  follows  in  regard  to  their  accelerating 
powers,  those  with  the  greatest  power  being  placed  first : 

Streptococcus.  \  M.  paratetrageims. 

Pneumococcus.  I  Staphylococcias  aureus. 

B.  influenzcB.  B.  diphtheria. 

M.  catarvhalis.  Staphylococcus  albiis. 

'B.  coli. 
The  experiments  which  enable  me  to  give  an  affirmative  answer  to 
question  {a)  likewise  afford  an  answer  in  the  positive  to  question  (6). 
To  question  (c)  I  am  not  yet  in  a  position  to  give  an  answer  in  either 
direction. 

Question  {d)  I  have  fully  investigated  for  all  bacteria  associated  with 
pulmonary  phthisis  which  are  considered  not  to  form  extra-cellular 
toxins,  and  have  found  that  cultures  of  bacteria,  even  of  many  weeks 
growth,  fail  to  produce  any  acceleration  upon  the  rate  of  growth  of  the 
tubercle  bacillus  if  these  cultures  are  sterilised  by  filtration  through 
Chamberland  candles  instead  of  by  the  aid  of  heat.  The  presence  of 
the  bacterial  elements  seems  essential  for  the  production  of  the  effect. 

Assuming  that  these  bacterial  toxins  are  able  to  exercise  the  same 
influence  in  the  human  body  as  the}^  do  under  artificial  conditions — and 
in  support  of  this  hypothesis  I  will  adduce  certain  evidence — it  then 
follows  that  the  mixed  infections  in  cases  of  pulmonary  phthisis  may 
play  a  two-fold  part,  viz. :  (i)  that  of  exerting  an  accelerating  influence 
upon  the  rate  of  multiplication  of  the  B.  tuberculosis,  and  (2)  that  of 
producing  the  results  which  we  have  learnt  to  associate  with  their 
presence  in  other  parts  of  the  body,  each  variety  of  bacterium  causing 
changes  peculiar  to  itself.  For  instance,  the  staphylococcus  is  known 
to  elaborate  three  substances  :  (i)  a  leucocidal  substance,  giving  rise  to 
cell  necrosis  and  liquefaction  of  the  tissues ;  (2)  an  endotoxin,  whose 
liberation  on  the  death  of  the  cocci  produces  a  general  as  well  as  a 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  I  5  3 

local  toxic  effect ;  (3)  a  hsemolysin,  to  which  the  body  almost  always 
contains  an  ample  antibody,  so  that  anemia  is  not  a  striking  charac- 
teristic of  staphylococcal  infection.  The  deduction  may  fairlv  then  be 
made  that  a  complicating  staphylococcal  infection  must  play  some  part 
in  cavity  formation  and  in  the  production  of  toxic  symptoms  ;  as,  how- 
ever, the  staphylotoxin  is  an  endotoxin  and  only  liberated  by  the  death 
and  lysis  of  the  bacteria,  the  toxic  effect  should  be  a  limited  one.  This, 
in  practice,  we  find  to  be  the  case;  high  pyrexia  is  only  exceptionally 
found  in  cases  in  which  pulmonary  tuberculosis  is  complicated  by  a 
pure  staphylococcal  infection. 

Again,  the  pneumococcus  appears  to  form  not  only  a  leucocidin 
and  a  powerful  endotoxin,  but  also  possibly  some  little  exotoxin  ; 
inasmuch  as  the  leucocidin  is  certainly  not  so  powerful  as  that  of  the 
staphylococcus,  while  the  toxins  are  considerably  more  potent,  it 
might  be  anticipated  that  with  a  concomitant  pneumococcal  infection 
cavitation  effects  would  be  rather  less  marked  and  toxic  effects  more 
marked  than  with  the  staphylococcus ;  this  appears  to  be  the  case. 

Again,  as  the  Micrococcus  catarvhalis  appears  to  give  rise  to  no 
leucocidal  substance  and  probably  to  no  exotoxin,  the  part  it  can  play 
in  the  causation  of  cavitation  and  pyrexial  symptoms  must,  therefore, 
be  a  small  one  ;  its  energies  are  devoted  to  the  production  of  catarrhal 
symptoms  ;  its  power  of  stimulating  the  rate  of  growth  of  the  tubercle 
bacillus,  as  judged  from  certain  test-tube  experiments,  would  appear  to 
be  considerable. 

Finally  the 5.  influenzcB^Novi\6.  appear  to  form  little  or  no  leucocidin, 
but  considerable  quantities  of  a  very  potent  endotoxin  ;  whether  it 
forms  exotoxin  is  not  known.  Its  influence  in  the  production  of 
cavities  should,  therefore,  be  small,  but  in  the  production  of  pyrexial 
symptoms  great.  Some  confirmation  of  this  is  afforded  by  clinical 
observations. 

•Inasmuch  as  we  have  learnt  from  the  preceding  experiments  that 
the  presence  of  a  concomitant  infection  does  not  necessarily  mean  the 
exercise  of  an  accelerating  influence  upon  the  growth  of  the  B.  tuber- 
culosis, either  owing  to  the  fact  that  the  micro-organism  in  question  is 
incapable  of  elaborating  such  a  stimulin  altogether,  or  because  the 
stimulin  it  does  form  is  ineffective  towards  the  particular  strain  of  the 
B.  tuberculosis  with  which  it  is  associated,  or  finally  because  the  latter 
is  incapable  of  stimulation  by  the  toxin  of  any  other  micro-organism, 
and  inasmuch,  moreover,  as  the  action  peculiar  to  the  associated  micro- 
organism may  by  no  means  necessarily  be  for  evil — for  instance,  the 
lytic  action  of  the  staphylococcus  may  not  necessarily  be  prejudicial 
to  the  patient,  but,  on  the  contrary,  may  lead  to  softening  of  the  foci, 
the  voiding   of   vast  numbers  of  the  tubercle   bacillus,  and    ultimate 


154  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

healing  of  the  cavity  so  formed — it  necessarily  follows  that  when  a  con- 
comitant infection  is  present  the  precise  role  played  by  each  of  the 
allied  invaders  should  be  accurately  determined.  Every  case  of 
pulmonary  tuberculosis  is  a  complete  law  unto  itself,  and  generalised 
deductions  are,  therefore,  fraught  with  danger. 

Careful  observation  has  convinced  me  that  in  the  most  rapid  cases 
of  pulmonary  phthisis,  such  as  the  miliary  and  broncho-pneumonic, 
mixed  infections  may  be  altogether  absent,  or  the  numbers  of  the 
associated  micro-organisms  relatively  to  those  of  the  B.  tuberculosis 
may  be  extremely  small.  It  does  not,  however,  necessarily  follow  that 
the  extremely  rapid  multiplication  of  the  tubercle  bacilli  is  not  due  to 
a  prior  manuring  of  the  soil,  say  with  the  toxins  of  the  pneumococcus 
or  B.  influenzcB  in  the  first  case,  or  that  the  supply  of  manure  furnished 
by  the  few  concomitant  invaders  in  the  second  place  is  altogether 
insufficient  or  is  ineffectual  in  producing  an  ill-effect. 

I  have  the  opportunity  of  determining  the  accelerating  effect  in  vitro 
of  the  secondary  invaders  upon  the  B.  tubei'culosis  from  one  case  only 
of  acute  broncho-pneumonic  phthisis.  The  experiments  were  not 
altogether  conclusive,  but  they  appeared  to  show  that  the  toxins  of  the 
associated  micro-organisms  produced  no  acceleration  on  the  growth  of 
the  associated  tubercle  bacillus. 

The  numbers  of  the  secondary  invaders  relativel}^  to  those  of  the 
tubercle  bacillus  in  specimens  of  sputum  voided  from  this  case  were 
extremely  small  from  the  inception  of  the  infection  to  the  very  end. 

On  the  other  hand,  in  the  case  illustrated  by  figs,  sg*"  and  39'', 
the  numbers  of  the  pneumococci  in  the  sputum  relatively  to  those  of 
the  B.  tuberculosis  were  also  very  small,  yet  we  see  how  great  was  the 
influence  of  the  toxin  of  the  former  upon  the  rate  of  multiplication  of 
the  latter. 

We  therefore  learn  if  these  cultural  experiments  have  any  definite 
value — and  this  I  hope  to  show  is  certainly  the  case — that  actual  numbers 
of  secondary  invaders  appearing  in  the  sputum  have  little  bearing  upon 
the  future  progress  of  the  case.  Their  true  importance  may  be  estimated 
by  cultural  experiments  and  observations  upon  the  patient  in  the 
manner  which  I  shall  now  describe. 


Method  of  Determining  whether  tJie  Deductions  made  from  Cidtural 
Observations  have  any  Value  when  applied  to  the  Human  Subject,  and 
the  Application  of  the  facts  so  Learnt  to  the  Prevention  and  Cure  of  con- 
comitant Infection. 

If  the  observations  made  in  vitro  hold  with  equal  force  in  regard  to 
the  human  body,  it  should  obviously  follow  that  if  a  concomitant  infec- 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  I  5  5 

tion  can  be  stamped  out  not  only  should  such  symptoms  as  are  directly 
referable  to  the  secondary  organism  or  organisms  be  caused  to  disappear, 
but  also  a  definite  effect  should,  in  most  instances,  be  produced  in 
course  of  time  upon  the  growth  of  the  tubercle  bacillus  itself. 

The  question  at  once  arises  in  any  given  case  of  phthisis,  is  it  possible 
to  determine  the  precise  role  that  is  being  played  by  allied  invaders  and 
the  tubercle  bacillus  respectively  ?  While  I  am  not  prepared  to  state 
that  this  can  always  be  accomplished,  in  many  cases  it  most  certainly 
can  be  done. 

The  method  depends  largely  upon  the  most  careful  stethoscopic 
examination  of  the  chest  and  the  detailed  observation  of  the  change 
in  physical  signs  produced  by  the  inoculation  of  therapeutic  doses  of 
autogenous  vaccines  and  of  tuberculin  respectively.  Inasmuch  as  the 
determination  of  the  precise  nature  of  the  concomitant  infection  is  not 
a  very  difficult  matter,  the  task  before  one  would  be  greatly  simplified 
if  the  exact  nature  of  the  physical  signs  which  may  be  produced  in  the 
chest  by  each  micro-organism  were  known  ;  this,  unfortunately,  is  not 
the  case. 

That  all  the  physical  signs  producible  by  the  B.  tuberculosis  +  a 
concomitant  infection,  with  the  single  exception  perhaps  of  those  of 
cavitation,  may  be  produced  by  a  perfectly  pure  infection  by  the  B. 
tuberculosis,  I  believe  to  be  the  case,  but  none  the  less  is  it  true  in  the 
great  majority  of  instances  that  by  far  the  greater  proportion  of  the 
physical  signs  which  most  clinicians  would  assign  to  the  action  of 
the  B.  tiibercidosis  are  in  reality  due  to  the  other  micro-organisms 
present. 

The  precise  part  played  by  the  B.  tuberculosis  and  by  the  allied 
organisms  respectively  is  determined  in  the  following  way. 

The  patient  is  confined  to  bed  under  the  most  favourable  conditions 
that  can  be  secured ;  the  temperature  and  pulse  are  recorded  four- 
hourl}^  and  the  daily  amount  of  sputum  measured.  Specimens  of  the 
sputum  are  examined  in  the  ways  already  indicated,  cultures  made  of 
the  B.  tuberculosis  and  of  all  the  secondary  invaders,  vaccines  and  toxin 
preparations  of  each  of  the  latter  prepared,  and  in  due  course  of  time 
the  accelerating  effect  of  the  toxin  of  each  associated  micro-organism 
observed. 

Daily  stethoscopic  examinations  of  the  chest  are  also  made  and  the 
observations  recorded  upon  a  suitable  chart ;  the  best  form  for  this 
purpose  is  the  diagrammatic  one  employed  here,  as  this  affords  ample 
room  for  the  insertion  of  such  signs  as  we  may  employ.  When  the 
patient  has  settled  down  into  a  more  or  less  constant  condition  as  regards 
pulse,  temperature,  physical  signs  and  expectoration,  by  which  time 
vaccines  should  have  been  prepared,  we  are  ready  to  proceed.     Obviously 


156  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

there  are  two  possible  ways  of  beginning*:  (i)  by  employing  tuberculin 
inoculations  and  observing  their  effects ;  (2)  by  employing  the 
vaccines  either  singly  or  in  combination  and  observing  their  effects. 
The  tuberculin  and  vaccines  should  never  be  employed  together 
as  the  effect  of  one  will  completely  mask  that  of  the  other.  Personally 
I  think  the  best  procedure  is  to  estimate  the  effect  of  the  vaccine 
before  that  of  the  tuberculin  and  to  employ  the  vaccine  of  one  organism 
at  a  time,  in  order  that  the  precise  influence  of  each  maybe  determined. 
To  this,  however,  there  is  one  prachcal  objection  to  which  reference 
will  be  made  later. 

Accordingly  the  physical  signs  in  the  chest  having  been  again  recorded 
a  therapeutic  inoculation  of  the  vaccine  is  performed,  such  dosages  as 
the  following  being  employed  :  (i)  B.  infliienzcz,  100  millions ;  (2) 
Staphylococcus,  100  millions  ;  (3)  B.  septus  or  other  diphtheroid,  100 
millions;  (4)  M.  catarrhalis,  50  millions;  (5)  M.  paratetragenus,  50 
millions  ;  (6)  B.  of  Friedlander,  50  millions  ;  (7)  B.  protetis,  50  millions  ; 
(8)  Streptococcus,  25  millions  ;  (g)  pneumococcus,  25  millions;  (10) 
B.  coli,  25  millions. 

As  a  second  examination  of  the  chest  should  be  made  in  about  twelve 
hours  it  is  most  convenient  to  select  an  hour  between  8  and  10  p.m.  for 
the  inoculation.  The  records  of  temperature  and  pulse  are  of  course 
continued,  and  the  sputum  measured  at  first  at  twelve-hourly  intervals, 
later  at  daily  ones.  Subsequent  observations  then  of  the  chest  are 
made  after  the  lapse  of  twelve,  twenty-four  and  forty-eight  hours  and 
daily  thereafter. 

If  the  organism  of  which  the  vaccine  was  employed  be  concerned  in 
the  production  of  signs  and  symptoms  and  the  dosage  employed  be 
adequate,  a  definite  effect  should  be  produced  in  any  one  or  more  of  the 
following  directions  within  twelve  hours  : 

(i)  There  may  be  rise  in  the  pulse-rate  of  10-20  beats; 

(2)  there  may  be  rise  in  the  temperature  of  o'5-i*5°  F. ; 

(3)  there  may  be  an  increase  in  the  quantity  of  sputum ; 

(4)  there  may  be  an  increase  or  alteration  in  the  physical  signs  ; 
and  of  these  the  last  is  the  most  important. 

Comparison  of  Charts  15"  and  15*  will  serve  to  illustrate  the  actual 
changes  so  produced  in  a  certain  case. 

Fresh  examination  at  the  end  of  twenty-four  hours  should  show  a 
swing  back  in  the  condition  of  the  patient : 

(i)  The  pulse-rate  should  be  the  normal  of  the  patient ; 

(2)  the  temperature  should  have  fallen  to  its  old  level  or  to  a 
lower  one ; 

(3)  the  sputum  may  be  diminishing ; 

(4)  the  physical  signs  should  be  improving,  and  may  correspond  to 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


D/ 


what  thev  were  before  the  inoculation  or  a  certain  amelioration   may 
have  been  produced  (Chart  15'')  ■ 

At  forty-eight  hours  the  changes  noted  after  twenty-four  hours 
should  have  advanced  further  in  the  same  direction  (Chart  15-^).  In 
some  instances  there  is  a  somewhat  delayed  reaction  :  the  changes  which 
are  described  above  as  being  typical  of  the  twelfth  hour  have  not 
been  evidenced  till  the  twenty-fourth  hour,  those  of  the  twenty-fourth 
hour  not  being  evidenced  till  the  forty-eighth  hour.  By  the  end  of 
seventy-two  hours  there  may  be  a  further  improvement  in  the  clmicai 
signs  of  the  patient  and  this  may  continue  for  several  days.  A  time 
will,  however,  come,  largely  dependent  on  the  dose  of  vaccine  given,  when 
instead  of  improvement  a  retrogression  will  be  initiated,  this  is  the 
signal  for  a  repetition  of  the  vaccine. 

Front   of  Chest  Back  of  Che^t 


POSTJUSSIC 
HALE 


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Chart  15". — Before  first  inoculation.     Sputum  =  6  oz.  per  day. 

Occasionally  it  will  happen  that  no  reaction  whatsoever  is  obtained; 
this  indicates  one  of  two  things,  either  [a)  that  the  dose  was  too  small, 
or  (6)  that  the  vaccine  itself  has  no  power  of  stimulating  the  formation 
of  immune  bodies.  If  the  former  alternative  be  thought  likely  a 
double  dose  is  given  at  the  expiration  of  seventy-two  hours  and 
observations  continued  as  before ;  this,  I  think,  should  alwavs  be  done 
before  assuming  the  latter  alternative,  (h)  that  the  vaccine  itself  is 
useless,  which  indicates  that  the  corresponding  organisms  are  producing 
no  effects  at  the  infected  foci,  and  that  trial  of  a  vaccine  of  another  of 
the  organisms  should  now  be  made. 

If  this  procedure  be  carefully  carried  out  it  will  be  found  that  in 
those  cases  in  which  the  secondary  infection  is  a  multiple  one,  there  is 
a  marked  difference  in  the  response  which  is  made  to  inoculations  of 
the  several  vaccines  :  that  some  produce  much  more  effect  upon  the 


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Chart  15*. — Twelve  hours  after  first  inoculation.     Sputum  =  10  oz.  per  day. 


Fi'ont  of  Chest 


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Chart  is"-'. — Twenty-four  hours  after  first  inoculation.     Sputum  =  6  oz.  per  day. 

front   of  Chest  Back  of  Chest 


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Chart  15''. — Forty-eight  hours  after  first  inoculation.     Sputum  =  2  oz.  per  day. 


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Chart  15". — Six  days  after  first  inoculation.     Sputum  =  3  oz.  per  day.     Second  inoculation. 


front   of  Chest 


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Chart  15A — Twelve  hours  after  second  inoculation.     Sputum  =  4  oz.  per  day. 


front   of  Chest 


Back  of  Cheat 


POST^TUSS'C 
RALE 


PR/l   TUSSIC 
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Chart  15^. —  Forty-eight  hours  after  second  inoculation.     Sputum  =  i  oz.  per  day. 


l6o  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

patient  generally  and  upon  the  physical  signs  in  particular  than  do 
others.  The  interesting  fact  now  comes  out  in  the  great  majority  of 
cases  that  the  vaccine  which  will  produce  the  greatest  effect  is  of  that 
organism  which  likewise  causes  in  vitro  the  greatest  acceleration 
upon  the  growth  of  the  B.  tuberculosis,  and  that  this  organism  is  not 
necessarily  the  one  which  predominates  either  in  smears  or  in  cultures 
of  the  sputum. 

It  is  thus  apparent  that  theoretically  the  way  in  which  the  fullest 
use  is  to  be  made  of  laboratory  observations,  and  according  to  which 
the  greatest  benefit  is  likely  to  accrue  to  the  patient,  provided  that  the 
clinical  condition  warrants  such  delay,  is  to  prepare  immediately 
vaccines  of  all  the  allied  organisms,  to  estimate  the  accelerating  influence 
of  the  toxin  of  each,  and  then  to  begin  treatment  with  the  vaccine  of 
that  organism  which  produces  the  greatest  accelerating  effect.  So  much 
time  has  been  occupied  in  the  preliminary  stages  of  these  investigations 
that  opportunity  for  the  application  of  the  lessons  learnt  has  as  yet 
been  scanty. 

In  the  instance,  however,  of  Case  2,  illustrated  by  figs.  40%  40'*, 
40^,  Plate  IX,  this  procedure  was  adopted,  with  the  striking  results 
that  are  depicted  in  Charts  16*^  to  16''. 

The  clinical  history  was  as  follows  : 

A  male,  aged  40  years,  had  had  practically  no  illness  till  two  years 
prior  to  my  seeing  him ;  enlarged  glands  then  appeared  on  the  right 
side  of  the  neck ;  suppuration  followed,  then  healing.  Nine  months 
later  a  severe  cough  came  on,  followed  by  pneumonia  and  pleurisy  for 
which  he  refused  to  take  to  bed  :  three  months  afterwards  tubercle 
bacilli  were  found  in  the  sputum.  Although  his  general  condition  had 
remained  good  his  appetite  had  become  very  bad,  and  there  had  been  a 
loss  of  weight  of  8  to  10  lbs.  There  had  been  no  night  sweats  and  the 
bowels  were  regular.  There  was  a  nightly  rise  of  temperature  to 
between  ioo°-ioi°  F. 

On  examining  the  patient  the  clinical  condition  briefly  was  as 
follows  :  In  the  mouth  eleven  stumps  were  seen  and  very  advanced 
pyorrhoea  alveolaris.  To  this  cause  the  enlarged  glands  were  attributed. 
These  ran  down  the  right  side  of  the  neck,  each  constituent  being 
about  the  size  of  a  hazel-nut. 

The  left  side  of  the  chest  moved  badly  and  was  somewhat  retracted, 
and  there  was  marked  sinking  in  over  the  left  clavicle.  There  was 
amphoric  resonance  from  the  first  to  the  fourth  left  ribs  in  front,  and 
below  the  level  of  the  nipple  there  was  marked  dulness. 

Behind  there  was  absence  of  resonance  above  the  clavicle,  and 
ver}'  marked  dulness  from  just  below  the  spine  of  the  scapula  to  the 
level  of  the  eighth  rib. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


i6i 


The  right  side  appeared  normal  back  and  front,  both  to  inspection 
and  percussion- 

On  auscultation  there  were  crackling  rales  to  be  heard  all  over  the 
left  chest,  back  and  front,  and  some  rhonchi  ;  over  the  space  in  front 
extending  from  below  the  first  rib  to  the  level  of  the  fourth  rib  cavernous 
rales  were  audible.  Here  also  there  was  bronchophony  and  marked 
pectoriloqu}^  The  only  abnormality  detected  on  the  right  side  was  a 
slightly  prolonged  expiratory  murmur  at  the  apex  in  front. 

The  diagnosis  was  made  of  advanced  phthisis  of  the  left  upper 
lobe  with  great  cavitation,  consolidation  of  the  whole  left  lower  lobe 
with  commencing  softening,  and  some  bronchitis.  Infection  of  the 
right  apex  doubtful. 


Front   of  Chest 


Back  o-f  Chest 


POST^TUSSIC 
RALE 


PRK.  -TUSSIC 
DRY-RALe 

oo 

ooo  - 
o 
PR/E.  -TUSSIC 

MO/ST- RALE 


XX  _ 
X    - 

RHONCtlUS 


C.'Cc^^rz  -6*/-- 


HI 


TV 


V 


2^j 


TT- 


r 


/ 


/Ji 


/^ 


o   o 


V 


0 


L 

o       o 

o 

R 

• 

0 

K    o 

0 

o 

I 

o     0 

O      0 

°      6 

n 

6 

o 

X 

m 

0 
o 

O         0 

K 

IV 

o 

0 

^0 

0      o 
0    ^ 

V 

\ 

o       o 
o 
o 

a      0 
o 

VI 

0 

o    o 
0 

o    0 
0 

vn 

Chart  i6". — Case  2,  before  inoculation  with  Vaccine  I. 


Specimens  had  previously  been  forwarded  to  me,  and  the  tubercle 
bacillus,  pneumococcus,  Streptococcus  longus  isolated. 

The  patient  was  sent  to  bed,  and  on  the  second  day  the  eleven 
stumps  and  few  remaining  sound  teeth  extracted  ;  the  sockets  were 
sprayed  repeatedly  with  hydrogen  peroxide,  and  a  chinosol  mouth- 
wash prescribed.  Three  days  later  the  patient  already  declared  that 
he  felt  better  and  that  his  appetite  had  improved. 

As  by  the  sixth  day  the  evening  temperature  had  remained  steady 
for  three  consecutive  days  at  99*8°  F.  and  the  morning  one  at  98*6^- 
98*8°  F.  it  was  resolved  to  begin  treatment  with  the  streptococcal 
vaccine.  Chart  16^  shows  the  then  existing  condition  of  the  chest.  A 
50-million  dose  was  given  at  7  p.m.,  and  subsequent  observations  made 
next  morning  at  9  a.m.,  at  7  p.m.  at  night,  and  at  7  p.m.  on  subsequent 
evenings.     Charts  16^,  IP,  etc.,  illustrate  the  findings. 

1 1 


Front   of  Chest 


Back  of  Cheat 


R. 

■^ 

o     O  a    c3 

^^ 

fOST^TUSSIC 

I 

><> 

n 

i 

4^' 

PR/f  -TUSSIC 
DRY-RA.LE 

m 

^ 

^ 

coo  = 
PRK  -TUSSIC 

IV 

V 

X 
X 

Ox 

XX  _ 
X    - 

KHONCMUS 

X   ,  <* 

0  > 

^ 

r'"'^ 

<J 

w    o 

^ 

R 

\^^^^ 

X  0 

7 

"'^r 

o  o 

JT 

<7 

2zr 

d  e> 

/K 

e>  X 

O    6 

V 

o  ^ 

> 

w 

o 

o5» 

0 

w: 

Chart  i6''. — Case  2,  fourteen  hours  after  inoculation. 


Front   of  Chest 


Back  oi  Chest 


POSr^Tvssic 

HALS 


fRK  TUSSIC 
DKY-KALB 

oo 

ooo  = 
o 
ff>/€  -TUSSIC 

MOIST-KAU 


XX  . 
X    - 

KHONCMUS 


R 

> 

^ 

o 

L 

^ 

I 

^ 

7"' 

> , 

n 

/ 

^ 

y 

^. 

"A 

r> 

o 
o 

IV 

o 
o 

O     0 

X 

0 

A 

0° 

Y 

<} 

o 
o 

0 

a 

L 

^ 

R 

'^^^ 

0 

■X 

o 

^    0 
o 

I 

o 

X 
0" 

R 

0    o 
X 

a   " 

o 

III 

o 

< 

0 

IV 

X 

o 

o 

'o' 

V 

o 
0 

o 

o 

VI 

YH 

Chart    i6^'. — Case  2,  twenty-four  hours  after  inoculation. 


Front   of  Chest 


Back  of  Chest 


POST^TUSSIC 
RALE 


PR/l   TUSSIC 
DRY -RALE 

OO 
ooo  = 
o 
PR/C  -TUSSIC 

'■iOlsr-RA.lE 


XX  . 

X    - 

-RHONChUS 


A 

> 

^ 

^ 

L 

^ 

I 

?^ 

'^K' 

p 

n 

7y 

> 

m 

> 

o 

IV 

o 

X 

K 

V 

o 

L 

o 

^ 

R 

o 

^ 

<J 

J 

o 

o 

o 

iT 

•3 

X 

o 

HI 

X 

a 
\ 

e 

IV 

o 
X 

o 
X 

e? 

V 

o 

o 

n 

VH 

Chart  16''. — Case  2,  five  days  after  first  inoculation. 


Front   of  Chest 


Back  of  Chest 


R. 

^ 

o 

L 

o^"^"*^^^ 

L 

o 

<o 

R 

:^ 

fOST-TUSSIC 

I 

V 

a; 

O 

o 

o 

o 

1? 

7 

o 
X 

•C7 

^  >^ 

iT 

n 

1^ 

^ 

':'y.  = 

^0 

m 

PRK   TUSSIC 
DRY -RALE 

m 

V 

« 

o 
X 

o 

o 

„". 

0 

/ 

IV 

oo 

ooo   = 

w 

o 

X 

x 

•^/P-f  -TUSSIC 

o 

o 
X 

V 

Y 

o 

X 

0 

o 

o 

C7 

*o 

vr 

fi:HONCHUS 

w: 

Chart  16". — Case  2,  six  days  after  first  inoculation  ;  second  inoculation  Vaccine  I. 


Front    of  Chest 


Back  of  Chest 


R. 

^ 

^^ 

/L 

-^ 

L 

:-- 

^ 

^ 

R 

\^ 

POST-TUSSIC 

I 

^ 

^V 

\ 

0 

I 

0 

X 

0 

" 

n 

n 

Yr 

0 

•;:;  = 

Cf 

0 

0    0 

0 

m 

PR/l   TUSSIC 

m 

c» 

/   0 

0 

CJ 

a 

0 

IV 

00 

000    = 

w 

0 

Pff/t  -TUSSIC 

V 

MOIST-RALE 

, 

Y 

yi 

XX  . 
X    - 

^HONCHUS 

MR 

Chart  i6^ — Case  2,  eleven  days  after  first  inoculation  ;  third  inoculation  Vaccine  II. 


Front   of  Chest 


Back  of  Chest 


POST-TUSSIC 
RAL£ 


.PRM.  -TUSSIC 
DRY-RALE 

00 

000  - 

PRK  -TUSSIC 
MOIST-RALE 


XX  . 
X    - 

/iHONCnUS 


R 

> 

^ 

"^ 

L 

-^ 

L 

'^ 

R 

> 

1 

V 

(2^ 

0 

0 
0 

0 

I 

n 

^ 

b 

0 

0  ■ 
X 

0    0 

0 

n 

0 
^0 

0 
0 

0 

m 

m 

0 

r/ 

0 
0 

0 
0 

0 

0 
0 
0 

IV 

— — 

IV 

0 

0 
0 

0   ° 
0 

0 

0 

-   0 

0     0 

0 

V 

Y 

VI 

w: 

Chart  16". — Case  2,  twelve  hours  after  third  inoculation. 


1 64 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


It  will  be  observed  that  at  the  end  of  fourteen  hours  there  was  some 
exacerbation  of  the  signs,  and  the  temperature  was  raised  o'5°  F.;  by 
the  end  of  twenty-four  hours  improvement  had  begun  to  set  in, 
although  the  temperature  was  still  raised  o'5°  F.  Thereafter  steady 
improvement  continued  till  the  evening  of  the  sixth  day,  when  there 
was  a  slight  exacerbation.  The  50-million  dose  of  streptococcal  vaccine 
was  accordingly  repeated,  with  the  result  that  a  similar  sequence  of 
effects  was  produced. 

On  the  twelfth  day  of  treatment,  although  there  were  no  signs  of 
relapse,  I  decided  to  give  a  50-million  dose  of  the  pneumococcal  vaccine, 


Front  of  Chest 


Back  o-f  Chest 


POST-TUSSIC 
RALE 


PR/l  -TUSSIC 
DRY-RALE 

000    = 
PR/E  -TUSSIC 
MOIST-RALE 


XX  . 

X    - 

KHONChUS 


R 

> 

^ 

L 

^ 

L 

^ 

R, 

I 

0 

y 

0 

I 

n 

'/ 

0 

0 

X 

n 

0 

X 

m 

m 

"0 

e 

0 

- 

IV 

IV 

^ 

V 

V 

n 

m 

Chart   16''. — Case  2,  fifteen  days  after  first  inoculation,  left  for  home  three  days  after  third 

inoculation. 


as  the  patient  had  to  return  four  days  later,  and  as  he  would  pass  out 
of  my  care  thereafter  I  thought  it  well  to  ascertain  the  value  of  this 
vaccine,  with  a  view  to  combining  it,  if  found  advisable,  v/ith  the 
streptococcal  one  for  employment  by  the  doctor  in  the  country. 

A  shght  increase  in  the  signs  was  noticed  twelve  hours  later  (Chart 
169),  but  this  rapidly  passed  off,  and  when  I  examined  the  patient  on 
the  morning  of  his  departure  {i.  e.  the  sixteenth  day)  I  was  more  than 
gratified  to  find  that  the  condition  was  that  depicted  in  Chart  16^. 
The  dulness  over  the  lower  lobe,  back  and  front,  had  completely 
gone,  the  amphoric  breathing,  bronchophony  and  pectoriloquy  were 
reduced,  and  only  a  very  occasional  small  rale  was  to  be  heard  any- 
where.    Even  post-tussic  rales  could  not  be  elicited  elsewhere. 

When  seen  four  months  later  the  patient  was  looking  and  feeling 
very  well  indeed  ;  he  had  recovered  all  his  lost  weight,  and  an  occa- 
sional fine  rale  at  the  end  of  inspiration  was  all  that  could  be  heard. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  1 65 

The  subsequent  history  of  the  patient  was  one  of  continued  pro- 
gress for  a  period  of  over  two  years,  interrupted  only  by  an  attack  of 
influenza,  which  soon  yielded  to  treatment,  and  by  a  slight  pyrexial 
attack  set  up  by  active  exercise  to  escape  the  attentions  of  a  very 
much  excited  bull.  He  then  contracted  a  severe  pneumococcal 
influenzal  infection,  neglected  himself,  and  soon  died. 

The  experience  I  had  in  this  case  of  the  effect  producible  by 
a  suitable  vaccine  has  been  confirmed  in  other  cases.  Inasmuch, 
however,  as  the  estimation  of  the  accelerating  effect  of  the  toxins 
occupies  about  ten  weeks  of  time,  and  this  delay  may  prove  anything 
but  advantageous  to  the  patient,  two  alternative  procedures  have  sug- 
gested themselves  : 

(i)  The  prior  estimation  of  the  action  of  tuberculin  upon  the 
physical  signs,  which  is  carried  out  in  precisely  the  same  way,  merely 
substituting  for  the  vaccine  such  doses  of  tuberculin  as  are  thought 
advisable ; 

(2)  The  more  or  less  empirical  employment  of  vaccines  of  some  or 
all  of  the  organisms  isolated  from  the  sputum,  choice  being  made  of 
combinations  which  experience  indicates  as  being  likely  to  benefit  the 
patient  :  this  empirical  choice  is  subsequently  confirmed  or  modified 
by  the  laboratory  experiments  and  by  the  progress  of  the  patient. 

The  latter  of  these  alternatives  I  consider  the  better,  inasmuch  as 
experience  tells  me  that  in  the  class  of  case  which  is  likely  to  benefit 
from  vaccine  treatment,  the  effects  produced  by  the  vaccines  are  much 
more  rapid  and  much  more  marked  than  would  be  those  produced 
by  any  limited  course  of  tuberculin  therapy. 

In  illustration  of  the  validity  of  this  position,  I  will  give  a  short 
description  (with  charts)  of  a  case  in  which  this  procedure  was 
adopted. 

Mrs.  A ,  aged  48  years.     History  briefly  as  follows  :  x\bout  five 

years  before  consulting  me  several  haemorrhages  from  the  lung.  Went  to 
Midhurst  for  five  months,  where  man}-  tubercle  bacilli  were  found,  and 
the  diagnosis  made  of  tuberculous  disease  of  both  lobes  of  the  right 
lung.  Improved  considerably,  and  told  she  was  almost  dry.  Went 
home,  and  almost  immediately  contracted  a  severe  bronchitis,  which 
threw  her  back.  Remained  at  home  under  open-air  treatment  for 
about  a  year,  then  went  to  Rosa  for  six  months.  The  high  altitude 
did  not  seem  to  suit  her,  so  returned  to  England  in  the  summer,  which 
she  spent  at  Margate.  Here  she  had  a  haemorrhage  from  the  bowel 
and  some  pvrexia,  which  persisted.  Since  then  she  had  stayed  in 
England,  spending  the  last  two  winters  at  Falmouth.  Despite  the  fact 
that  she  has  had  much  mental  worry,  she  was  more  than  holding  her 
own.     Unfortunately  last  winter   she  was  placed  in  a  damp  bed,  con- 


i66 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


tracted  influenza,  had  several  haemorrhages,  and  lost  ground  consider- 
ably. This  influenzal  attack  she  has  been  unable  to  throw  off.  Her 
usual  rectal  temperatures  have  been  g8°  in  the  morning,  99°  in  the 
evening;  sometimes  100°  in  the  evening,  and  occasional!}'  101° — this 
vi'hen  she  contracts  a  cold,  and  to  these  she  is  very  subject. 

Her  periods  are  regular,  the  evening  temperature  rising  about  06° 
for  the  preceding  six  or  eight  days  and  while  they  last,  then  falling  to 
her  normal.  She  has  not  lost  weight,  in  fact  the  tendency  to  increase 
is  such  that  she  limits  the  amount  of  milk  and  cream  in  her  dietary  to 
counteract  it.  When  I  saw  her  she  had  been  in  bed  for  about  two  months 
and  looked  rather  pale,  but  otherwise  in  robust  health.  Tubercle  bacilli 
were  very  numerous  in  her  sputum,  allied  invaders  being  the  B.  influcnzco. 


'front   of  Chest 


Back  of  Che^t 


R. 

L 

^^ 

POSTjTUSSie 

I 

^A 

'/y 

r 

^"0 
0   „ 

0 

0 

n 

A 

/ 

PR/l  -TUSSIC 
DRY-RALE 

0'" 
0  . 

0  ^ 
0   . 

0 

m 

y 

^/* 

' 

00 

000  = 
0 
f/f/E  -TUSSIC 

^  0 
0  • 

0 

e 

IV 

/. 

y/ 

V 

XX  . 
X   - 

KHONCHUS 

Chart  17". — Mrs.  A — ,  before  inoculation  with  vaccine- — B.  Influenza    lOO  millions,  M.  catar- 
rhalis,  50  millions,  pneumococcus  and  streptococcus  each  25  millions. 

M.  catarrhalis,  Streptococcus  brevis  and  Pneumococcus.  Her  tem- 
perature rose  in  the  evening  to  about  ioo°  F. 

The  main  points  revealed  by  clinical  examination  of  the  chest  were 
as  follows  :  it  was  well  covered,  there  was  no  sinking  in  above  the 
clavicles  or  elsewhere  ;  the  respiratory  movements  were  poor,  especially 
on  the  right  side. 

On  percussion  there  was  impaired  resonance  in  front  above  the 
right  clavicle  and  in  the  first  space,  and  over  the  whole  of  the  right 
chest  behind.  Elsewhere  it  was  not  quite  satisfactory  without  being 
actually  defective. 

On  auscultation  the  condition  shown  in  Chart  ly"  was  found.  In 
front  on  the  left  side  was  bad  air-entry  from  the  clavicle  to  the  fifth 
rib;  in  the  second  and  third  space  an  occasional  clicking  rale  was  heard 
at  the  end  of  expiration;  in  the  fifth  and  sixth  spaces  external  to  the 


Front   of  Chest 

R.  ^.^       r —       L 


Back  oi  Chest 


POST^TUSSiC 
HALE 


XX  . 
X    - 

RHONCHUS 


L 

^ 

R 

' 

/ 

I 

/ 

n 

y 

/ 

/ 

m 

/ 

/ 

/ 

IV 

m 

/ 

/ 

TP^ 

o 

/ 

W        -'o 

'  o 

o 

w: 

*   # 

-    a 

o 

Chart  17*. — Mrs.  A — ,  eighteen  hours  after  inoculation. 


Front   of  Chest 

R.         ^^       r-^       L 


Back  of  Chest 


PR/C  -TUSSIC 
MOIST-RALE 


XX  . 
X    - 

KHONCnUS 


-^»<w^ 


/ 


/ 


R 


m 


IV 


VI 


w: 


v4 


^/> 


Chart  17'-.— Mrs.  A—,  five  days  after  first  inoculation  ;  similar  condition  on  twenty-sixth  day. 


Front    of  Chesi 


Back  of  Chest 


R. 

^ 

^ 

L 

.^ 

POST^TUSSIC 

X 

-  /    • 

I 

X 

n 

^ 

c«*    *« 

^ 

PR/l  -TUSSIC 

y. 

m 

00 
000  = 

Pff/E  -TUSSIC 

/ 

.d 

/ , 

IT 

MOIST-RALE 

/. 

K 

y 

V 

/^ 

<ra**> 

X^ 

XX  . 
X   - 

RHONCHUS 

/ 

/ 

/ 

L 

^ 

^ 

0/^ 

0  ' 

0,' 

.-. 

'y^ 

y  ' 

I 

' 

'/^ 

7^ 

^ 

M 

0-0 

0      0 

'0 

0 

.y 

y 

y- 

m 

>:: 

-  .  0 

'0 

' 

IV 

/*    0 

V 

0  • 

VI 

0 

'    - 

YH 

• 

•   t 

Chart  ly. — Mrs.  A  —  ,  eighteen  hours  after  fourth  inoculation,  which  equalled  one  and  a  half 
times  initial  dose.     Looking  pale  and  "  feeling  rather  out  of  sorts." 


Front 
R.    ^^^ 

Qf  Chest 

z. 

Back  of  Chest 

POsr^Tussic 

X 

I 

/ 

I 

K 

n 

■> 

^^ 

*^ 

■^^•^^ 

u 

0 

0 

0 

/ 

V 

m 

0 

0 
/ 

PPJf.  -TUSSJC 
DRY-RALE 

A 

m 

/ 

0 

IV 

(^'0 

'• 

000  = 

w 

0 

PRK  -TUSSIC 

0 

0 

V 

\//> 

/ 

V 

t 

^«< 

^ 

vr 

X. 

y 

#/^ 

fy 

"/ 

KHONCtlUS 

/ 

T2r 

-7- 

T^'— 

Chart  17". — Mrs.  A — ,  forty-eight  hours  after  fourth  inoculation. 


Front   of  Chest 


Back  of  Chest 


posr^wssic 

fiAL£ 


PR/l  -TUSSIC 
DRY -RALE 

00 
000  = 
o 
PRK  -TUSSIC 

■  MOIST-RALE 


XX  . 
X    - 

fiHONCtlUS 


R 

> 

■>        0 

^ 

L 

X 

V 

/ 

/ 

/ 

n 

/ 

;ncc 

j£c>^ 

'^ 

m 

A 

ey4- 

7 

IV 

/ 

/ 

V 

' 

y 

L 

-^ 

^ 

R 

:^ 

I 

X 

^ 

>f 

^ 

^ 

n 

0 

0 

0 

-  /^-. 

^ 

m 

K 

c 

/' 

V 

IV 

^ 

V 

\£j 

w 

wr 

Chart  17A — Mrs.  A — ,  before  sixth  inoculation  1  of  double  initial  dosage). 


Front   of  Chest 


Back  of  Chest 


R. 

0 

L 

^ 

POST-JUSSIC 
RALE 

/ 

^ 

^ 

n 

RRA   TUSSIC 
DRY-RALE 

m 

00 
000  ~ 
0 
PP/t  -TUSSIC 

IV 

V 

XX  . 
X    - 

JiHONCnuS 

L 

^ 

> 

^ 

■ 

<? 

1^ 

7 

;•. 

, 

• 

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Chart  17*. — Mrs.  A — ,  twenty-two  hours  after  ninth  inoculation. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


169 


nipple  line  there  was  '•  sticky  ^'  breathing.  On  the  right  side  in  the 
second,  third  and  fourth  spaces  there  were  whistling  ra/^s,  especially 
noticeable  in  the  axillary  line.  Behind  there  was  bad  air-entry  over  the 
whole  left  chest,  with  an  occasional  moist  rale  from  the  second  to  the 
seventh  space.  Over  the  whole  of  the  right  side  from  below  the  level 
of  the  clavicles  there  were  whistling  rales,  and  in  the  fourth  and  fifth 
spaces  near  the  middle  line  tubular  breathing  was  to  be  heard  over  an 
area  nearly  three  inches  square.  An  autogenous  vaccine  was  prepared, 
and  an  initial  dose  containing  100  milHon  B.  influenzcE,  50  million  M. 
catarvhalis  and  25  million  each  pneumococcus  and  Streptococcus  brevis 


was  given. 


Front  of  Chest 


Back  of  Chest 


R. 

^ 

L 

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fOSTrTUSSIC 

I 

n 

fiR/i  -TUSSIC 
DRY -RALE 

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PPK  -TUSSIC 

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XX  . 
X    - 

RHOlKlUS 

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R 

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yn 

Chart  17/-. — Mrs.  A — ,  forty-eight  hours  after  ninth  inoculation. 


Opportunities  for  making  the  regular  and  methodical  examinations 
which  I  have  already  described  as  so  advisable  were  lacking,  but  the 
progress  of  the  case  can  be  sufficiently  well  followed  in  the  various  charts. 
Twentv-four  hours  after  this  inoculation  the  condition  of  the  chest  was 
as  shown  in  Chart  17'-':  there  had  been  a  marked  clearing  of  the  chest  : 
the  fact  that  this  happened  so  rapidly,  taken  in  conjunction  with  the 
fact  that  there  was  practically  no  general  reaction,  showed  that  the  dose  if 
anything  erred  rather  on  the  small  side  ;  still,  as  the  improvement  con- 
tinued and  there  was  no  retrogression  five  days  after  inoculation  (see 
Chart  17O,  the  dosage  was  maintained  and  repeated,  as  also  on  the 
twelfth  and  nineteenth  days.  It  was  reported  to  me  on  the  twenty-sixth 
day  that  no  moist  sounds  were  to  be  heard  in  the  chest,  that  the  area 
of  tubular  breathing  was  smaller,  but  that  the  air-entry  was  still  bad 
and  that  the  state  of  the  chest  might  fairly  be  considered  to  be  that  repre- 
sented  in   Chart    17'.      I    therefore  advised    that    the   dosage    for  the 


I/O  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

fourth  inoculation  should  be  increased  by  one  half  and  saw  ihe  patient 
eighteen  hours  later.  The  reaction  was  very  marked  (see  Chart  17^')  ; 
numerous  rales  were  to  be  heard  above  the  right  clavicle  and  a  few  in 
the  first  right  space  in  front.  The  whole  right  chest  behind  was  filled 
with  coarse  rales  and  rhonchi,  while  on  the  left  side  behind  fine  rales 
were  to  be  heard  in  the  first,  second  and  third  spaces  at  the  end  of 
expiration.  These  signs,  however,  quickly  subsided,  the  condition 
forty-eight  hours  after  inoculation  being  that  shown  in  Chart  17*. 

This  dosage  was  accordingly  repeated  eight  days  later  and  as  there 
was  only  a  quite  moderate  resultant  reaction  on  the  following  days 
double  the  initial  dose  was  given  at  the  sixth  administration.  This 
produced  no  general  reaction  and  no  flaring  up  of  the  clinical  signs 
comparable  to  that  brought  about  by  the  fourth  inoculation  ;  on  the 
contrary  a  slight  but  definite  improvement  resulted  and  persisted  for 
the  subsequent  six  days,  when  this  dosage  was  repeated.  Once  again 
the  increase  of  physical  signs  was  very  slight. 

Subsequently  the  area  of  tubular  breathing  steadily  diminished,  the 
temperature  failed  to  rise  above  gg'^,  the  sputum  became  much  reduced 
in  quantity,  and  the  patient  was  soon  able  to  get  about  the  house  and 
maintain  her  steady  improvement.  It  will  be  seen  from  Chart  17^ 
that  practicaHy  the  whole  of  the  clinical  signs  in  this  case  cleared  up 
under  the  exhibition  of  bacterial  vaccines  alone,  and  when  it  is  remem- 
bered that  this  is  a  case  of  quite  long-standing  phthisis  it  serves  well 
to  illustrate  what  I  have  already  alluded  to,  viz.,  the  impossibility  of 
ever  saying  beforehand  how  much  of  the  signs  are  due  to  the  infection 
by  the  B.  tiihercnlosis  and  how  much  to  the  mixed  infection. 

As  soon  as  large  doses  of  vaccine  entirely  fail  to  produce  any 
immediate  reaction  or  any  further  improvement  in  the  patient  I  shall 
advise  that  treatment  be  begun  with  tuberculin,  and  be  controlled  in 
precisely  a  similar  manner.  A  discussion  of  the  tuberculin  therapy 
of  the  case  does  not  fall  within  the  scope  of  this  chapter,  but  attention 
may  be  drawn  to  the  fact  that  suitable  doses  of  tuberculin  will 
certainly  elicit  responses  in  this  chest  and  produce  reactions  therein, 
signs  becoming  obvious  within  twelve  to  twenty-four  hours  where 
none  were  existent  at  the  time  of  inoculation. 

The  fact  that  all  physical  signs  have  disappeared  in  a  chest  is  by  no 
means  proof  of  the  disappearance  of  all  infection.  They  have  so  de- 
parted from  this  chest,  but  vaccines  can  hardly  have  influenced  the 
infection  by  the  tubercle  bacilli,  and  these  are  still  being  discharged  in 
the  sputum. 

This,  then,  has  been  the  method  of  choice  which  I  have  followed 
during  the  past  two  to  three  3^ears  in  the  treatment  of  all  cases  of 
pulmonary  phthisis  which  have  passed  through   my  hands.      I   have 


THI-:    ISACTERIAL    DISEASES    OF    RESPIRATIOX.  IJI 

been   enabled   to  demonstrate  the  changes  to  numerous  medical  men 
well  skilled  in  the  use  of  the  stethoscope  and  to  two  or  three  specialists 
in  pulmonary  tuberculosis  ;  their  observations  of  the  changes  produced 
have  been  described  in  such  terms  as  "  staggering  "  and  "  absolutely 
incredible  if  not  observed  for  oneself,"  and  such  indeed  the  changes  are 
that  are  often  brought  about  by  the  administration  of  suitable,  skilfully 
prepared  vaccines  in  adequate  dosages  at  suitable  intervals.     But  let 
it  not  be  thought  that  dramatic  changes  such  as  these  can  be  secured 
in  everv  case.     Sometimes — and  this  even  when  the  laboratory  deter- 
minations show  subsequently  that  there  is  no  lack  of  accelerating  action 
upon  the  growth  of  the  tubercle  bacillus  by  the  allied  toxins — progress 
is  relatively  slow  :  slight  reactions  are  obtained,  but  the  return  wave 
does  not  carry  the  patient  much  past  the  starting-place.     A  little  gain 
after  each  inoculation,  however,  means  a  considerable  gain  by  the  end 
of  four  to  six  months,  and  little  by  little  the  desired  result  is  brought 
about.     The  important  point  to  be  remembered  is  that  so  long  as  a 
distinct  reaction  is  produced  in  tweh'e  to  twenty-four  hours  there  should 
be  no  increase  of  dosage  ;  even  if  the  resultant  improvement  after  six 
to  eight  days  is  hardly  perceptible,  that  dosage  which  is  effective  in 
regard  to  the  production  of  reaction  must  be  persisted  in  till  it  shows  a 
marked  tendencv  to  prove  ineffective,  when  it  may  be  doubled.     The 
fact  that  four  or  five  inoculations,  each  productive  of  an  adequate  reac- 
tion, do  not  appear  to  produce  a  satisfactor}'  advance  in  the  condition 
of  the  patient  is  eminently  suggestive  that  the  vaccine  is  not  a  complete 
one,  some  organism  not  being  included  in  it  which  is  of  considerable 
importance  in  the  setiology  of  the  condition.     A  thorough  examination 
of  the  sputum  should  elucidate  this  point.      The  practice  of  making 
systematic  examinations  of  the  sputum  every  fortnight  is  strongly  to  be 
advocated  as  tending  to  exclude  such  a  cause  of  failure.     It  by  no  means 
follows  in  a  case  of  multiple  infection  that  a  complex  vaccine,  however 
skilfully  blended  at  the  beginning,  wall  prove  efficient  to  the   end  of 
treatment.     It  is  a  phenomenon  constantly  encountered  that  in  mixed 
infections  one  organism  will  be  more  easily  eradicated  than  another, 
and  that  as  one  organism  dies  out  another  comes   to  the   front  ;  for 
instance,  in  mixed  influenza-pneumococcal  infections  at  the  beginning 
of  treatment  there  may  be  in  a  unit  mass  of  sputum  loo  .000  B .  tnfluenzcB 
and  100  pneumococcus;  at  the  end  of  a  month's  treatment  these  figures 
may    be    1000    B.   influenzce   and    100  pneumococcus.     This  does   not 
indicate  total  failure  to  produce  immunity  against  the  pneumococcus. 
That  the  pneumococcus  or  its  toxin  produces  a  very  marked  acceleration 
in    growth    of   the  B.   inflnenzcE  I    have  often   demonstrated,  and  the 
marked  reduction  in  the  numbers  of  the  B.  influew^cB  may  well  indicate 
a  reduction  in  this  effect  referable  to  the  pneumococcus.  and  so  perhaps 


172  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

a  reduction  in  the  pathogenicity  and  vitality  of  the  pneumococcus  as 
well  as  an  increase  in  antibodies  to  the  B.  infliienzcB  referable  to  the 
inoculations  of  B.  inflnenzcB  vaccine.  None  the  less  a  good  effect  will 
usually  ensue  upon  increased  dosage  of  the  pneumococcal  vaccine,  that 
of  the  B.  infliLenzcB  being  maintained. 

Or,  again,  when  the  vaccine  was  first  prepared  the  numbers  of  some 
one  or  more  organisms  may  have  so  enormously  preponderated  over 
those  of  another  variety  that  either  the  presence  of  the  latter  altogether 
escaped  notice,  or  its  isolation  proved  to  be  impossible.  In  such  a 
case  the  exhibition  for  six  to  eight  weeks  of  the  vaccine  first  prepared, 
although  a  well-marked  reaction  follows  each  administration,  may 
result  in  no  apparent  or  well-marked  improvement  in  the  clinical 
condition  of  the  patient.  Examination  of  the  sputum  will  almost 
surely  show  that  the  vaccine  has  not  been  without  effect ;  the  organisms 
of  which  the  vaccine  is  composed  may  have  almost  disappeared,  but 
the  one  which  previously  could  not  be  isolated  has  come  so  much 
to  the  front  that  it  has  sufficed  to  maintain  the  clinical  condition  more 
or  less  in  its  original  state ;  the  exhibition  of  a  fresh  vaccine  of  this 
organism  will  almost  certainly  produce  the  desired  result. 

In  view  of  these  facts  I  personally  prefer  to  keep  my  several  vaccines 
separate  in  a- case  of  multiple  infection,  and  blend  them  in  the  required 
dosages  prior  only  to  each  inoculation. 

Another  disturbing  factor  which  will  be  revealed  by  methodical 
examination  of  the  sputum  is  the  acquirement  of  a  totally  new  infection. 
This  is  especially  liable  to  occur  during  catarrhal  epidemics,  and  may 
prove  a  source  of  great  trouble.  The  old  vaccine  upon  which  perhaps 
the  patient  was  doing  so  well  may  have  to  be  discarded  and  a  fresh  one 
prepared  to  meet  the  emergency.  When  the  catarrhal  infection  has 
been  overcome  the  resumption  or  not  of  the  old  vaccine  will  be  deter- 
mined by  a  bacteriological  examination.  An  occurrence  such  as  this 
proves  not  only  so  disturbing  to  the  patient,  but  often  so  prejudicial 
that  no  effort  should  be  spared  to  obviate  it.  Two  measures  which  I 
have  found  most  effective  are  {a)  the  prevention  of  access  to  the  patient 
of  all  sufferers  from  acute  nasal  or  bronchial  catarrhs ;  (&)  the  periodic 
immunisation  of  the  patient  against  acute  catarrhs.  This  is  best  done 
by  the  administration  every  six  months  of  the  50,  100,  and  250  million 
doses  of  the  combined  vaccine  for  colds  of  the  Wimpole  Institute;  the 
three  doses  being  given  in  ascending  series  at  intervals  of  seven  to  eight 
days  (see  also  p.  183). 

"  But,"  it  may  be  asked,  "  do  all  cases  of  mixed  infection  of  phthisis, 
when  treated  with  the  appropriate  vaccine  or  vaccines  under  careful 
control  as  to  dosages  and  intervals  by  the  clinical  and  bacteriological 
methods  which  have  been  described,  respond  favourably  to  treatment  ?  " 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  1 73 

M}^  answer  to  this  is,  omitting  for  the  present  those  cases  in  which 
vaccine  treatment  appears  definitely  to  be  contra-indicated,  that  there 
would  appear  to  be  a  small  number  of  cases  in  which  no  apparent  good 
results  from  such  a  course  of  treatment.  I  have  myself  met  with  only  one 
such  case.     This  I  will  first  describe,  and  then  attempt  the  explanation. 

Miss  B ,  aged  37  years,  early  in  igoo  contracted  pleurisy.      In 

December,  igoo,  T.B.  discovered  in  sputum.  Went  to  Mentone,  where 
her  voice  became  husky.  On  her  return  a  few  months  later.  Dr. 
Greville  MacDonald  found  tuberculous  laryngitis.  Local  treatment  did 
not  prove  very  successful.  Went  to  Neyland  Sanatorium  from  January, 
igo2,  to  March,  igo3,  where  her  voice  improved.  The  pulmonary 
condition,  which  was  confined  to  the  right  upper  lobe,  remained  almost 
stationary.  Went  to  live  at  Clacton.  By  October,  1907,  the  voice 
had  become  so  husky  and  breathing  so  difficult  that  Dr.  Greville 
MacDonald  performed  tracheotomy.  Early  in  igo8  she  returned  to 
Neyland  for  six  to  seven  months.  In  June,  igog,  her  voice  began  to 
improve,  and  b}-  January,  igio,  had  become  fairly  strong. 

When  I  saw  her  she  complained  chiefly  of  a  very  bad  cough,  and 
of  great  difficulty  in  voiding  the  rather  scanty  but  very  purulent 
sputum  ;  she  was  very  thin,  and  her  appetite  was  very  bad.  At  the 
right  apex  in  front  there  was  cavernous  breathing  with  bronchophony 
and  pectoriloqu}' — only  a  few  dry  rales  were  audible.  Over  the  right 
apex  behind  there  was  impaired  resonance,  and  an  occasional  rale  was 
to  be  heard. 

As  Dr.  Greville  MacDonald  was  not  available,  I  sent  her  to  Mr.  G.  S. 
Hett  for  examination  of  her  larynx.  He  reported  advanced  disease  of 
the  left  side,  with  oedema  of  the  right  side  and  of  the  inter-arytenoid 
cartilage. 

Examinations  of  her  sputum  showed  great  numbers  of  tubercle 
bacilli  and  of  Staphylococcus  alhtis,  no  other  organisms  being  detected. 

This  was  obviously  a  case  of  very  slowly  progressive  phthisis  and 
tuberculous  lar3mgitis. 

Into  a  full  account  of  the  treatment,  which  was  continued  for  two 
years,  I  do  not  propose  to  enter.  Tuberculin  T.R.  and  B.E.  and  a 
vaccine  of  Staphylococcus  albus  were  employed.  Opportunities  for 
making  the  careful  clinical  observations  which  I  have  already 
described  as  so  advisable  were  lacking,  so  that  I  was  not  in  a  position 
to  determine  how  far  and  in  what  way  the  patient  responded  to  the 
vaccine.  I  can  only  say  that  she  appeared  to  make  slow  but  steady 
progress;  this,  however,  I  quite  convinced  myself  was  referable,  if  to 
the  treatment  at  all,  solely  to  the  tuberculin.  Although  the  staphylo- 
coccus vaccine  was  persisted  with  and  utilised  in  dosages  varying  from 
100  to  4000  million  organisms,  it  never  seemed   to  produce   the  least 


174  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

effect  upon  the  staphylococcus  infection  ;  if  anything,  the  numbers  of 
this  organism  showed  a  slight  increase.  The  amount  and  character 
of  the  sputum  showed  no  alteration,  except  in  a  reduction  in  the 
numbers  of  the  tubercle  bacilli  :  these  had  almost  disappeared  when 
the  patient  contracted  a  severe  pneumococcal-influenzal  infection — her 
first  catarrhal  infection  during  two  years — and  succumbed  in  less  than 
three  weeks. 

As  personally  I  had  never  seen  such  an  utter  failure  on  the  part  of 
a  vaccine  to  influence  in  the  lung  or  any  other  part  of  the  body  a 
bacterial  infection  I  endeavoured  to  elucidate  the  cause,  and  for  this 
purpose  devised  the  laboratory  experiments  I  have  already  described. 
The  vaccine,  I  may  mention,  was  several  times  re-made,  to  eliminate 
the  possibility  of  errors  in  its  manufacture.  The  experiments  taught 
these  interesting  points  : 

(i)  That  the  toxin  of  this  particular  Staphylococcus  albus  was  abso- 
lutely without  an  accelerating  influence  upon  the  rate  of  growth  of 
this  particular  tubercle  bacillus — if  anything,  there  was  a  very  slight 
inhibitory  action.  I  repeated  this  experiment  three  or  four  times,  re- 
making the  toxm  and  employing  fresh  batches  of  culture  medium, 
always  with  the  same  result  (c/.  figs,  42^  and  42'',  Plate  X). 

(2)  That, this  Staphylococcus  albus  toxin  was  capable  of  markedly 
stimulating  the  growth  of  the  strains  of  the  B.  tuberculosis  derived  from 
other  cases  of  pulmonary  phthisis. 

(3)  That  the  rate  of  growth  of  this  particular  tubercle  bacillus 
could  not  be  influenced  by  toxins  whose  powers  of  stimulation  upon 
other  strains  of  the  tubercle  bacillus  had  been  repeatedly  demonstrated 
(cf.  figs.  42%  42'',  42'\  Plate  X). 

The  only  conclusion  was  that  there  was  some  subtle  property 
probably  peculiar  to  the  patient's  tissues  which  had  so  modified  the 
tubercle  bacillus  as  to  render  it  incapable  of  stimulation  by  bacterial 
toxins,  and  which  rendered  nugatory  all  attempts  to  produce  an  arti- 
ficial immunity  to  the  Staphylococcus  albus. 

In  this  connection  I  may  remark  that  the  observation  has  been 
made  by  numerous  clinicians  that  cases  of  pulmonary  phthisis  compli- 
cated by  a  Stapliylococcus  albus  infection  frequently  run  a  very  chronic 
course.  I  have  even  heard  of  cases  still  living  in  whom  cavitation  was 
observed  and  Stapliylococcus  albus  found  over  thirty  years  ago. 

So  far  as  I  am  aware  this  is  no  general  rule,  and  it  does  not  appear 
to  hold  for  a  Staphylococcus  aureus  infection.  There  is  thus  a  rough 
•correspondence  with  the  nature  of  the  cutaneous  lesions  produced  by 
these  respective  organisms. 

In  any  future  cases  which  I  may  be  called  upon  to  treat  in  which 
the   Staphylococcus  albus  is  the  sole  accessory  microbe  my  procedure 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  1 75 

will  probably  be  as  follows  :  to  begin  treatment  immediately  with  the 
staphylococcus  vaccine,  but  if  no  good  appears  to  be  resulting  by  the  time 
that  the  laboratory  observations  are  completed,  and  these  reveal  a  lack 
of  accelerating  power  on  the  part  of  the  staphylococcal  toxin,  I  shall 
discontinue  the  vaccine  and  rely  upon  tuberculin  alone. 

It  may  here  be  mentioned  that  I  do  not  consider  the  use  of  combi- 
nations of  vaccine  and  tuberculin  to  be  advisable;  vaccine  and  tuber- 
culin each  are  capable  of  producing  their  definite  effect  upon  the 
physical  signs,  an  effect  which  can  be  accurately  determined.  If  a 
combination  be  employed  it  is  quite  impossible  to  tell  what  precise 
effect  each  is  producing,  and  all  guidance  as  to  dosages  and  intervals 
is  lost.  In  cases  where  mixed  infection  is  present  the  better  procedure 
would  appear  to  begin  with  suitable  doses  of  the  vaccine  of  that 
particular  accessory  microbe  which  experience  indicates  as  likely  to  be 
a  predominant  factor  in  the  production  of  the  physical  signs,  or  with  a 
suitable  combination  of  vaccines,  and  continue  with  this  treatment 
according  to  the  lines  which  I  have  indicated  until  laboratory  investi- 
gations have  determined  the  accelerating  effect  of  each  toxin.  If  no 
accelerating  action  is  observed  and  the  patient  is  not  improving  to 
discontinue  vaccines  and  employ  tuberculin. 

If  improvement  is  resulting,  and  laboratory  observations  enable  the 
allied  organisms  to  be  sorted  out  into  those  with  an  accelerating  influence 
and  those  without,  to  continue  with  the  vaccines  of  the  organisms 
which  fall  into  the  former  category.  The  appropriate  time  to  resort  to 
tuberculin  in  these  cases  would  appear  to  be  when  the  vaccines  cease 
to  produce  further  marked  amelioration  ;  if  it  be  done  sooner  difficulties 
are  sure  to  arise,  for  when  the  patient  begins  to  retrogress  a  little  after 
each  inoculation — signal  for  a  fresh  inoculation — a  difficulty  arises  in 
deciding  whether  the  fresh  stimulus  that  is  required  is  that  to  the  forma- 
tion of  antibodies  to  the  tubercle  bacillus  or  to  the  allied  organisms. 
Experience,  however,  is  as  yet  very  limited,  and  dogmatic  expressions 
of  opinion  are  much  to  be  deprecated.  As  I  have  said  before,  every 
case  of  phthisis  is  a  law  unto  itself,  and  what  may  prove  the  right  course 
for  one  patient  may  be  quite  the  wrong  one  for  another. 

The  class  of  case  in  which  vaccine  treatment  is  likely  to  prove 
of  little  avail  is  unfortunately  that  for  which  its  services  are  most 
required — I  mean  the  cases  of  widely  disseminated  broncho-pneumonic 
phthisis.  Mixed  infection  is  rarely  absent  in  these  cases,  but  the 
number  of  accessory  microbes  present  is  as  a  rule  extremely  small. 
Pneumococcus  and  streptococcus  are  those  most  commonly  found. 

In  the  lobar  form  of  acute  pneumonic  phthisis  vaccines  may  or 
may  not  prove  of  service.  In  cases  which  begin  as  this  variety 
vaccines  are  likely  to  prove  an  invaluable  standby,  but  when  this  form 


1/6  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

supervenes  upon  a  chronic  attack  vaccine  treatment  can  hardly  be 
anticipated  to  delay  the  end.  The  pneumococcus  and  Bacillus 
influenza  are  the  accessory  microbes  most  likely  to  initiate  this  change 
of  type. 

Summary  of  my  Observations  and  Conclusions  upon  the  Influence  of  Mixed 
Infections  in  Phthisis  and  upon  their  Cure  by  means  of  Vaccines. 

(i)  The  allied  micro-organisms  found  in  phthisis  may  be  either  the 
truly  primary  infection,  in  which  case  they  have  initiated  the  tuber- 
culous process  by  a  prior  manuring  of  the  soil,  or  they  may  be 
secondary,  in  which  case  they  exert  not  only  an  action  upon  the  tissues 
peculiar  to  themselves,  but  also,  at  times,  an  accelerating  effect  upon 
the  rate  of  multiplication  of  the  tubercle  bacilli. 

(2)  The  question  whether  vaccine  treatment  will  prove  of 
advantage  to  the  patient  or  without  effect  may  be  indicated  by  the 
result  of  determinations  as  to  whether  the  toxins  of  the  accessor}^ 
invaders  produce  any  acceleration  in  the  rate  of  growth  in  vitro  of  the 
autogenous  tubercle  bacilli. 

(3)  The  treatment  of  cases  should  be  begun  with  an  autogenous 
vaccine,  or  mixture  of  vaccines,  the  precise  influence  of  each  dose  being 
estiniated  by.measurements  of  the  sputum,  temperature  and  pulse-rate, 
and  by  the  effect  produced  upon  the  clinical  signs  in  the  chest.  That 
dosage  is  an  effective  one  which  within  twelve  hours  produces  a  slight 
increase  in  the  amount  of  sputum,  slight  rise  of  temperature  and 
pulse-rate,  and  definite  increase  of  physical  signs.  If  these  have  passed 
off,  or  are  beginning  to  pass  off,  in  twenty-four  hours  the  dosage  is  an 
appropriate  one,  but  if  no  backward  swing  be  evidenced  within  forty- 
eight  hours  excess  of  dosage  is  thereby  indictaed. 

The  signal  for  repetition  of  the  inoculation  is  a  beginning  recru- 
descence in  the  signs  and  symptoms  ;  the  indication  for  increased  dosage 
a  failure  to  react  or  an  inadequate  reaction  on  the  part  of  the  patient. 
Periodical  bacteriological  examinations  of  the  sputum  are  highly  neces- 
sary to  eliminate  fresh  infections  or  an  increased  activity  on  the  part  of 
one  of  the  accessory  microbes,  due  possibly  to  the  removal  of  the  inhi- 
bitory action  which  may  have  been  possessed  by  a  variety  which  has 
been  eliminated. 

(4)  Tuberculin  and  vaccine  should  not  be  given  in  combination,  as 
the  effect  of  one  may  mask  the  effect  of  the  other,  and  confusion  is  sure 
to  arise  in  estimating  the  influence  of  a  given  dosage,  and  the  necessity 
for  re-inoculation.  Tuberculin  should  be  withheld  until  marked  im- 
provement has  been  made  under  the  exhibition  of  the  vaccine  and  the 
patient  is  remaining  more  or  less  stationary,  or  until  the  conclusion  has 
been  reached  that  vaccine  treatment  is  not  likely  to  produce  a  good  result. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  I  7/ 

The  tubercle  bacillus  and  various  allied  invaders  may  each  initiate 
changes  in  the  lung  tissues  which  give  rise  to  symptoms  practically  in- 
distinguishable. In  chronic  phthisis  with  mixed  infection  the  clinical 
signs  of  activity  may  be  almost  entirely  due  to  the  secondary  invaders. 
In  such  cases  the  proper  exhibition  of  the  suitable  vaccine  or  mixture 
of  vaccines  may  produce  an  amelioration  of  the  condition  which  is  very 
striking. 

While  it  is  perhaps  the  general  rule  that  the  allied  invaders  play 
the  principal  part  in  the  production  of  the  signs  and  symptoms,  it  is 
unwise  to  assume  that  this  is  always  so.  Careful  adherence  to  the 
procedure  which  I  have  described  will  soon  give  indication  that  a  change 
of  treatment  from  vaccine  to  tuberculin  is  advisable. 

(5)  Experience  is  j^et  too  limited  to  justify  any  dogmatic  expression 
of  opinion,  but  it  would  appear  that  in  vaccine  treatment  we  have  a 
most  valuable  adjunct  to  other  methods  of  treatment  of  cases  of  pul- 
monary tuberculosis  complicated  by  accessory  microbes.  Pyrexia  and 
frequency  of  pulse  may  be  reduced,  the  appetite  and  weight  increased, 
exacerbations  and  complications  diminished,  and  great  reduction  in  the 
physical  signs  brought  about,  so  that  large  areas  of  lung-tissue  which 
appeared  to  be  deeply  invaded  by  the  B.  tuberculosis  may  finally  give 
no  stethoscopic  evidence  of  involvement;  the  way  having  thus  been 
paved  for  the  employment  of  tuberculin,  if  this  be  indicated  or  found 
to  be  necessary,  a  more  rapid  and  more  complete  cure  should  then 
be  obtained  in  a  considerable  proportion  of  cases. 

It  will  perhaps  not  be  out  of  place  to  make  some  short  excerpts 
from  well-known  treatises  on  tuberculosis  wherein  the  authors  give 
their  opinions  of  the  scope  and  value  of  vaccine  treatment  in  the 
mixed  infections  of  pulmonary  tuberculosis. 

In  Diseases  of  the  Lungs,  edit.  5,  p.  627,  Powell  and  Hartley  say: 

"  We  have  given  reasons  for  believing  that  in  certain  rapidl}^  pro- 
gressive cases  of  phthisis  the  fever  and  the  spread  of  the  disease  are 
due  in  part  to  the  agency  of  organisms  other  than  the  tubercle  bacillus, 
which  at  least  prepare  the  way  for  the  activity  of  the  latter,  and  the 
question  arises  whether  by  isolating  such  organisms  from  the  sputum 
and  producing  appropriate  vaccines  their  activity  may  not  be  cut 
short,  to  the  relief  of  the  patient  and  the  improvement  of  his 
symptoms.  In  the  few  cases  known  to  us  which  have  been  treated  on 
these  lines,  the  results  have  been,  as  a  rule,  disappointing,  but  in 
the  following  case  (described)  some  improvement  was  apparently 
effected." 

They  conclude,  "  The  treatment  is  still  in  its  infancy,  it  is  based 
on  scientific  lines,  and  it  is  one  which  demands  a  careful  trial." 

In   Tuberculosis,  edited  by  Klebs  (igog),  p.  5g8,  Webb  summarises 

12 


178  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

as  follows  the  results  in  fifty  cases  inoculated  by  him  with  homologous 
vaccines  prepared  from  the  mixed  organisms  : 

"  (i)  In  no  case  has  a  patient  been  harmed  ; 

"  (2)   Many  patients  have  had  exacerbations  more  rarely  ; 

"  (3)  Expectoration  in  nearly  all  cases, has  been  lessened  ;  nocturnal 
coughs  have  frequently  been  eliminated ; 

"  (4)  In  some  cases  a  chronic  catarrhal  hoarseness  has  entirely 
disappeared ; 

"  (5)  Concomitant  pus  affections  have  cleared  away,  such  as 
suppuration  of  ears,  staphyloccoccic  acne  and  sycosis  ; 

"  (6)  When  these  vaccines  have  been  combined  with  small  doses  of 
Koch's  new  tuberculin,  spreading  infiltrations  have  been  averted  and 
cleared  up  ; 

"  (7)  In  a  case  which  displayed  tubercle  bacillus,  streptococcus, 
pneumococcus,  staphylococcus  and  M.  catarrhalis,  the  latter  was 
entirely  eliminated  by  appropriate  vaccine,  and  the  amount  of  sputum 
was  reduced  from  4  oz.  to  less  than  i  oz.  daily  ; 

"  (8)  Evacuations  of  4  to  6  oz.  of  sputum  daily  have  in  several 
cases  been  reduced  to  less  than  i  oz. 

"  The  impression  has  been  gained  that  the  bronchorrhcea  type  of 
cases  has,  perhaps,  received  less  benefit  connected  with  the  reduction 
of  sputum  than  the  cavernous  type. 

"  In  conclusion  the  author  would  put  forth  the  earnest  plea  that 
these  potent  remedies  be  used  early,  while  the  machinery  of  the 
immunisation  is  yet  unworn,  and  that  they  be  added  to  the  tuberculin 
treatment.  Then  the  ranks  of  the  advanced  tuberculous  will  be 
lessened." 

Pottenger  {Pulmonary  Tiiherciilosis,  1908,  pp.  257  and  261)  says  : 

"  In  the  treatment  of  advanced  cases  of  pulmonary  tuberculosis 
we  are  often  able  {i.  e.  by  general  methods)  to  arrive  at  a  result  which 
is  very  satisfactory  compared  with  the  condition  at  the  beginning  of 
treatment.  We  can  often  secure  a  healing  of  all  but  a  small  focus, 
which  keeps  on  secreting  month  after  month.  In  such  cases  it  seems 
probable  that  if  we  could  but  combine  with  tuberculin  the  appropriate 
vaccine  made  from  the  culture  of  the  associated  microbes  we  might 
heal  these  lesions  completely.  I  believe  we  are  safe  in  assuming  that 
mixed  infection  is  a  factor  in  all  cases  of  tuberculosis  which  have 
passed  beyond  the  early  stage  of  the  disease  and  arrived  at  the  open 
stage.  I  do  not  mean  by  this  that  an  open  surface  in  the  air- 
passages  is  necessary  for  this  association  of  other  bacteria,  for  they 
should  be  as  able  to  gain  entrance  to  the  tissues  without  an  ulcerated 
surface  as  easily  as  tubercle  bacilli,  but  I  mention  this  open  stage  as 
showing  a  disease  which  is  somewhat  advanced.     I  do   not   doubt  but 


THE    BACTERIAL    DISEASES    OE    RESPIRATIOX.  I  79 

that  the  true  remedv  for  mixed  infection  will  be  obtained  in  a  \accine 
made  from  the  cultures  taken  from  the  strain  of  the  micro-organism 
found  in  each  individual  patient.  The  results  which  we  had  so  far  in 
our  endea\-our3  to  treat  in  this  manner  are  very  encouraging." 

Bonnev  {Pulmonary  Tubercitlosis,  1910,  pp.  gii-giS)  gives  a  xevy 
good  account  of  the  results  he  obtained  in  twenty-eight  cases: 

'■'  In  group  5  are  embraced  patients  exhibiting  the  persisting  fever 
of  mixed  infection  who  were  subjected  to  injections  of  homologous 
vaccines  without  tuberculin  therapy.  There  are  twenty-eight  patients 
in  this  class  displaying  active  tuberculous  processes  with  profound 
constitutional  disturbance.  The  vaccines  were  not  administered  to 
any  patient  in  this  group  until  the  futilit}'  of  h3-gienic  measures 
without  specific  medication  had  been  demonstrated  beyond  question. 
In  view  of  the  fact  that  the  mixed  infection  is  often  the  determining 
factor  in  turning  the  scales  irretrievably  against  recover}-,  it  was 
deemed  justifiable  to  resort  to  the  use  of  bacterial  vaccines  for  patients 
apparentlv  doomed  to  a  fatal  termination.  An  earl\-  control  of  the 
septiceemia  ottered  the  only  rational  basis  for  hope  regarding  nearh-  all 
invalids  included  in  this  group.  .  .  .  All  individual  vaccines  were  pre- 
pared from  cultures  grown  from,  the  secretions  of  the  patient.  In  nearly 
all  cases  the  disease  had  been  of  long  standing,  the  duration  having 
been  less  than  one  year  in  but  three  instances.  While  a  few  patients 
had  been  under  obser^•ation  from  time  to  time  during  a  period  of 
sex-eral  years,  the  acute  septic  manifestations  had  been  of  comparatively 
brief  duration.  .  .  .  It  is  important  to  note  that  the  twenty-eight 
cases  are  divided  into  two  general  subdivisions,  the  first  twenty-two 
comprising  one  class,  and  the  last  six  another.  Among  the  patients  in 
the  former  the  physical  condition  was  extremely  urgent  in  all  cases, 
the  prognosis  very  unfavourable  in  five,  doubtful  in  two  and  utterh' 
hopeless  in  fifteen. 

"  In  these  cases  the  vaccine  medication  was  employed  in  a  last  effort 
to  reduce  temperature  and  possibly  aid  thereby  in  saving  or  prolonging 
hfe. 

"  In  the  second  sub-g^roup  very  satisfactory  improvement  had  been 
secured  in  each  instance.  The  nutrition  was  excellent,  with  complete 
absence  of  fever,  almost  entire  arrest  of  the  activity  of  the  tuberculous 
process  and  a  uniformly  good  prognosis.  In  these  cases,  however,  the 
cough  and  expectoration  represented  important  disturbing  features. 
In  noting  the  results  of  vaccine  therapy,  it  is  necessar}-  to 
discriminate  between  the  apparently  hopeless  cases  of  one  class  and 
those  without  temperature  elevation  or  other  grave  features  in  the 
second  group.  Of  the  twenty-two  cases  in  the  former,  all  of  whom 
bv  virtue  of  every  consideration  ordinaril\-  influencing  prognosis  were 


I  80  ■        THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

destined  to  an  early  fatal  termination,  eight  are  recorded  as  having 
achieved  improvement  to  such  an  extent  as  to  justify  an  unqualifiedly 
favourable  prognosis,  with  almost  complete  arrest  of  the  tuberculous 
process.  Thus  in  more  than  one  third  of  the  cases  the  entire  clinical 
picture  was  unexpectedly  transformed,  following  vaccine  medication. 
In  six  patients  there  was  observed  at  iirst  a  material  improvement,  but 
this  was  followed  by  a  subsequent  retrogression,  death  taking  place  in 
each  instance,  although  in  one  case  as  a  result  of  a  sudden  pulmonary 
haemorrhage.  In  seven  instances  no  appreciable  results  were  observed 
following  the  vaccine  medication  and  the  patients  finally  succumbed  to 
the  disease. 

"  In  the  second  class,  comprising  six  cases  exhibiting  a  favourable 
prognosis,  the  vaccine  was  administered  solely  in  the  hope  of  controlling 
distressing  cough  and  lessening  expectoration.  In  one  case  the  results 
were  highly  gratifying,  but  in  the  remaining  five  not  the  slightest 
influence  could  be  properly  attributed  to  the  vaccine.  These  results 
suggest  a  much  more  limited  field  of  usefulness  for  the  homologous 
vaccines  in  afebrile  cases  than  in  those  with  acute  septic  manifesta- 
tions. While  generalising  statements  in  connection  with  clinical 
observations  of  this  character  are  hardly  appropriate,  the  evidence 
appears  conclusive  that  some  benefit  may  be  expected  to  attend  the 
employment  of  such  an  agent  in  a  fair  proportion  of  cases  otherwise 
adjudged  incapable  of  improvement." 

Reference  to  Bonney's  table  is  necessary  in  order  to  appreciate  the 
striking  nature  of  the  results  achieved  in  some  of  the  cases. 

The  prevention  of  mixed  infection. — That  prevention  is  better  than 
cure  is  the  soundest  of  axioms,  and  obviously,  if  it  is  possible  to 
prevent  the  occurrence  of  any  mixed  infection  complicating  a  pulmo- 
nary tuberculosis,  this  is  a  much  better  procedure  than  eliminating  it 
when  it  has  occurred.  To  this  end  it  is  necessary  to  consider  the  way 
in  which  infection  by  other  bacteria  than  the  tubercle  bacillus  arises  in 
the  lung.  Bacteria  may  be  carried  to  the  lung  in  any  of  three  ways, 
(i)  via  the  respiratory  tract,  i.  e.  either  carried  in  the  air  current  or  by 
direct  extension  along  the  passages;  (2)  via  the  blood-stream;  (3)  by 
direct  extension  or  via  the  lymphatics  from  some  other  internal  focus, 
such  as  the  abdominal  peritoneum. 

Instances  of  bacteria  which  reach  the  lungs  in  the  first  way  are 
certainly  the  streptococcus,  M.  catarrhalis,  M.  ietragenus  and  paratetra- 
genus,  B.  septus,  diphtheroid  bacilli,  staphylococcus,  and  probably  the  B. 
proteus  and  B.  pyocyaneus;  and  sometimes,  if  not  usually,  the  pneumo- 
cocciis  and  B.  influenzce. 

Those  which  may  reach  the  lung  via  the  blood-stream  are  the 
pneiimococcus  and  B.  inftttenzce,  while  one  which  perhaps  usually  reaches 


THE    BACTERIAL    DISEASES    OF    RESPIRATION. 


I8l 


them   by  direct  extension  via   the    diaphragmatic    lymphatics   is    the 
B.  coli. 

The  origin  of  these  various  bacteria  and  the  mode  of  their  extension 
may  be  considered  with  advantage ;  and  in  this  connection  it  at  once 
suggests  itself  that  all  these  bacteria  may  be  divided  into  three 
categories :  (i)  those  purely  catarrhal  in  function  ;  (2)  those  purely 
pyogenic  ;  (3)  those  which  are  intermediate,  sometimes  producing 
catarrhal  symptoms,  sometimes  giving  rise  to  pus-formation. 


Catarrhal  organisms. 
Af.  catarrhalis. 
M.  paratetragetms. 
B.  septus. 
B.  influenzff. 


Pyogenic  organisms. 

Staphylococcus. 
B.  proteiis. 
B.  pyocy  aliens. 
B.  coH. 


Intermediate. 

Streptococcus. 
Pneumococcus. 


It  accordingly  follows  that  the  focus  from  which  the  mixed  infection 
has  arisen  must  have  been  either  a  catarrhal  or  a  suppurative  one.  If 
we  except  the  B.  coli,  whose  ingress  to  the  lung  is  probably  determined 
by  the  occurrence  of  a  diaphragmatic  pleurisy  or  of  a  peritonitis  which 
perhaps  has  caused  very  little  symptoms,  we  are  at  once  struck  by  the 
thought  that  all  the  organisms  which  complicate  cases  of  pulmonary 
tuberculosis  are  precisel}^  those  which  cause  common  pathological 
conditions  about  the  mouth,  nose,  naso-pharynx,  upper  and  lower  air- 
passages.  The  bacteria  and  the  conditions  they  give  rise  to  may  be 
tabulated  as  follows  : 


Organism. 
Streptococcus. 


M.  catarrhalis. 


Pneumococcus. 


M.  paratetragetms. 
Staphylococcus. 


B.  influefizce 

B.  of  Fried  lander. 


Conditions  in  which  they  may  be  concerned. 

Post-nasal  catarrh,  pyorrhoea  alveolaris,  follicular 
tonsillitis,  bronchitis,  asthma,  suppurative  condi- 
tions in  the  mouth  generally. 

Nasal  and  post-nasal  catarrh,  pyorrhoea  alveolaris, 
follicular  tonsillitis,  laryngitis,  and  tracheitis,  bron- 
chitis, asthma. 

Nasal  and  post-nasal  catarrh,  pyorrhoea  alveolaris, 
follicular  tonsillitis,  laryngitis,  tracheitis,  and 
bronchitis,  asthma,  pneumonia,  infections  of  the 
accessory  sinuses. 

Nasal  catarrh,  laryngitis,  tracheitis  and  bronchitis. 

Pyorrhoea  alveolaris,  post-nasal  catarrh,  tonsillitis  and 
quinsy,  suppurative  conditions  in  the  mouth 
generally. 

Nasal  catarrh  and  infections  of  the  accessory  sinuses, 
tracheitis,  bronchitis  and  pneumonia. 

Nasal  and  post-nasal  catarrh,  bronchitis,  pneumonia. 


152  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

Organism.  Conditions  in  which  they  may  be  concerned. 

B.  proteus.  Suppurative  conditions  of  the  accessory  sinuses  and  of 

the  mouth  generally. 
B.  pyocyaneus.  Suppurative  conditions  of  the  accessory  sinuses  and  of 

the  mouth  generaUy. 
B.  septus.  Nasal  and  post-nasal  catarrh  and  pharyngitis. 

If  we  except  those  rare  cases  of  pneumonia  and  bronchitis  which  do 
not  originate  in  a  catarrh  of  the  upper  passages,  it  at  once  becomes 
evident  that  the  conditions  of  prime  importance  are  catarrhs  of  the 
upper  passages,  pyorrhoea  alveolaris  (and  carious  teeth),  tonsillitis  and 
suppurative  conditions  of  the  mouth  generally  ;  and  it  therefore  follows 
that  those  measures  which  are  likely  to  preclude  the  occurrence  of 
mixed  infection  in  the  lung  are  those  which  are  directed  to  the  removal 
of  these  pathological  conditions  if  they  exist,  or  to  the  prevention  of 
their  occurrence  if  they  do  not  already  exist.  Due  attention  must 
therefore  be  paid  to  the  hygiene  of  the  mouth,  carious  teeth  must  be 
removed  or  stopped,  pyorrhoea  alveolaris  treated  by  a  competent  dentist, 
infective  conditions  of  the  tonsils  and  naso-pharynx  dealt  with 
adequately,  the  surgeon's  help  being  requisitioned  if  necessary, 
sufficient  airway  ensured  in  the  nasal  passages,  and  the  various 
catarrhal  coriditions  attended  to.  So  much  importance  do  I  attach  to 
the  observance  of  these  points  that  I  make  it  an  invariable  rule  to 
refuse  to  undertake  the  treatment  of  any  tuberculous  subject  who 
declines  the  prior  adequate  treatment  of  any  of  the  above  conditions. 
It  is  little  use  trying  to  eradicate  a  M.  catarrhalis  infection  of  the  lung 
when  a  condition  of  follicular  tonsillitis  in  which  this  organism  is 
concerned  is  allowed  to  exist  unchecked,  or  to  eradicate  a  streptococcal 
infection  when  from  acutely  pyorrhoeic  foci  fresh  streptococci  are  being 
constantly  outpoured  to  re-infect  the  pulmonary  tissues.  No  member 
of  the  community,  and  above  all  one  predisposed  to  phthisis  or  the 
victim  already  of  an  early  attack,  should  omit  to  have  periodical 
examinations  made  as  to  the  condition  of  the  oral  hygiene.  Ensure 
healthy  mouths  and  stamp  out  catarrhal  attacks  and  mixed  infections 
of  phthisis  would  be  no  more.  The  former  desideratum  is  easily 
attainable,  but  how  are  catarrhal  infections  to  be  obviated  ?  It  is  hardly 
possible  for  us  all  to  reside  in  polar  regions,  where  they  tell  us  such 
things  are  unknown,  or  even  to  reside  under  ideal  conditions  of  air, 
sunshine  and  food.  If  adequate  airway  be  ensured  and  correct  methods 
of  breathing  taught  a  considerable  step  is  taken  towards  prevention, 
but  this  does  not  suffice  for  a  very  large  proportion  of  mankind  : 
susceptibility  to  catarrhal  attacks  seems  to  be  an  almost  universal 
prerogative.  Some,  however,  are  more  susceptible  than  others.  To 
the  majority  the  usual  catarrhal  attack  may  be  but  an  inconvenience — 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  1 83 

sometimes  it  is  more,  and  means  an  acute  pneumonia  or  a  chronic 
bronchitis,  but  to  the  phthisic  it  is  an  event  of  the  utmost  importance. 
Life  under  ideal  conditions  does  not  suffice,  although  by  toning  up 
the  system  generally  it  certainly  does  tend  to  mitigate  the  severity  of 
the  attack,  but  something  more  than  this  is  necessary ;  any  procedure 
which  aims  at  less  than  total  prevention  is  inadequate. 

But  can  this  be  done  ?  I  think  it  can.  I  have  now  had  nearly 
ten  years''  experience  in  the  production  of  immunity  against  catarrhs, 
and  there  are  now  many  hundred  cases  which  have  either  been 
immunised  by  myself  or  according  to  my  directions.  When  I  state 
that,  so  far  as  I  can  ascertain,  the  result  among  those  with  whom  my 
instructions  are  carefully  followed,  is  that  in  go  per  cent,  at  least  80  per 
cent,  of  the  catarrhal  attacks  from  which  in  previous  years  they  suffered 
are  completely  obviated,  I  believe  I  am  understating  the  benefit 
derived  from  this  treatment.  In  many  cases  complete  immunity  is 
secured.  It  is  hardly,  however,  within  the  scope  of  this  chapter  to 
enter  into  a  full  discussion  of  the  procedure  and  its  results  in  regard 
to  the  susceptible  members  of  the  human  race  in  general ;  it  is 
necessary  to  consider  merely  the  procedure  to  be  followed  in  those 
already  the  victims  of  pulmonary  tuberculosis.  Not  only  in  the  United 
Kingdom  but  also  in  other  parts  of  the  world  there  seem  to  be  two 
severe  and  one  mild  epidemic  of  so-called  colds  annually.  In  England 
the  severe  ones  come  about  the  middle  or  end  of  October,  and  the 
middle  of  February  or  beginning  of  March  :  the  mild  one  occurs  at 
about  the  height  of  summer. 

Such  immunity  as  is  to  be  secured  by  preventive  inoculation  can  be 
obtained  in  about  sixteen  days,  and  lasts  according  to  the  individual  for 
four  to  eight  months.  If  a  catarrhal  attack  is  to  be  forestalled  it  therefore 
follows  that  treatment  should  be  commenced  at  the  beginning  of 
October,  February  and  July.  The  appropriate  dosages,  administered 
at  intervals  of  about  seven  days,  are  as  follows  : 

B.  septus.    Pneumococcus.      B.  infliienzcB. 

ist  dose      100     .  50         .  100 

2nd  dose    250     .         100         .  250 

3rd  dose     500     .        250         .     500-1000 

x\s  a  condition  of  lowered  immunity  sets  in  within  an  hour  or  two 
and  persists  over  a  period  of  12-18  hours  it  is  obviously  the  best  plan 
to  perform  every  inoculation  either  when  the  patient  is  in  bed  or 
on  the  way  home,  in  which  latter  case  he  should  dine  lightly  and 
retire  early  :  if  rest  in  bed  till  the  following  mid-day  be  possible  so  much 
the  better,  but  this  is  not  an  absolute  essential.      I,  however,  advise  a 


M.  catar- 

.¥. 

para- 

Strepto- 

rhalis. 

tetragenus. 

coccus 

50 

• 

50       . 

•          50 

100 

100 

.       100 

250 

250       . 

250 

1 84  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

little  extra  care  in  avoiding  damp,  cold  and  draughts  during  the  twenty- 
four  hours  ensuing  upon  an  inoculation. 

During  the  past  three  years  of  the  fifty  tuberculous  cases  which  I 
have  either  treated  myself  or  of  which  I  have  directed  the  treatment, 
only  four,  I  believe,  have  contracted  a  single  catarrhal  attack,  and  each 
of  these  had  through  force  of  circumstances  failed  to  undergo  immunisa- 
tion for  over  six  months — in  each  case  the  infection  was  a  pneumo- 
coccal-influenzal one,  and  the  highest  dosage  of  influenza  vaccine  which 
any  of  them  had  received  was  250  millions.  Now  I  consider  that  full 
immunity  against  the  influenza  bacillus  cannot  be  secured  with 
dosages  of  less  than  500  millions,  and  that  those  of  1000  millions  are 
even  preferable.  A  little  malaise,  quickened  pulse,  rise  of  a  degree  in 
temperature  and  perhaps  a  little  headache,  all  passing  away  within 
eighteen  hours,  are  the  only  ill-effects  I  have  ever  seen  result  from  this 
procedure. 

Upon  three  occasions  I  have  had  patients  at  sanatoria  at  which 
there  occurred  severe  catarrhal  infections;  the  reports  were  made  to 
me  that  my  patients  were  the  only  ones  that  failed  to  be  attacked. 

It  will  be  observed  that  in  the  vaccine  I  have  recommended  above 
no  B.  of  Friedlander  is  included  :  the  reason  for  this  is  that  this 
organism  has"  not  appeared  in  England  for  some  years  to  give  rise  to 
catarrhal  epidemics;  for  the  time  at  least  its  energies  are  in  abeyance  ; 
and  it  is  perhaps  as  well  to  stimulate  the  immunising  mechanism  of 
the  tuberculous  in  as  few  directions  as  possible.  F'or  this  latter  reason 
also  a  sHghtly  modified  programme  may  be  adopted,  viz.  :  for  those 
who  are  concerned  with  their  care  to  keep  themselves  well  informed  of 
the  onset  of  catarrhal  epidemics  and  of  the  precise  bacteria  to  which 
they  are  to  be  attributed  and  to  have  the  appropriate  mixture  of  vaccines 
at  once  compounded  and  utilised  in  the  immunisation  of  their  patients. 
This  procedure  has  the  merit  of  exciting  the  formation  of  as  few 
specific  anti-bodies  as  possible,  but  it  has  these  demerits :  (i)  a 
catarrhal  attack  may  forestall  knowledge  of  its  impending  presence ; 
(2)  adequate  immunity  is  certainly  not  to  be  anticipated  from  the 
first  inoculation,  and  hardly  from  the  second  ;  the  slight  increase  in 
immune  bodies  due  to  the  first  inoculation  may  not  suffice  to  ward  off 
an  attack.  It  is  perhaps  best,  therefore,  to  err  on  the  side  of  safety 
and  follow  closely  the  procedure  first  described. 

Should,  despite  all  precautions,  a  phthisical  individual  contract  an 
acute  catarrh,  bronchitis  or  pneumonia,  it  is  obviously  advisable  to 
limit  its  severity  as  much  as  possible.  This  is  best  done  not  only  by 
employing  such  general  measures  as  experience  has  shown  to  be  of 
use,  but  also  by  subjecting  the  patient  to  a  course  of  specific  immunisa- 
tion  with    autogenous  vaccine.      Here    I    should   again  mention  the 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  185 

extraordinary  tendency  of  certain  organisms,  notably  the  pnetnnococcus, 
B.  infliienzce  and  some  strains  of  streptococcus,  to  persist  in  the  lung 
tissues  long  after  all  symptoms  have  apparently  disappeared.  This  is 
true  both  for  the  tuberculous  and  the  non-tuberculous,  but  especially 
for  the  former,  and  to  these  it  is  a  matter  of  even  greater  moment  than 
to  the  latter.  The  way  in  which  these  organisms  may  persist  is  well 
illustrated  by  two  recent  experiences  of  mine.  A  patient  was  sent  to 
me  by  Dr.  H.  O.  Brookhouse,  the  symptoms  complained  of  being 
recurrent  pyrexial  attacks  of  short  duration,  accompanied  by  pro- 
found depression  and  a  tendency  to  faint  ;  between  these  attacks  the 
patient  was  apparently  perfectly  well.  The  only  clue  to  the  mystery, 
for  several  well-known  consultants  had  failed  to  diagnose  the  case, 
was  afforded  by  a  history  of  a  right-sided  pneumonic  attack  twelve 
years  previously.  This  time  corresponded  with  the  onset  of  a  severe 
influenza-pneumococcal  epidemic,  and  as  I  was  well  conversant  with 
the  tendency  of  these  bacteria  to  take  up  their  permanent  abode  in  the 
pulmonary  tissues,  I  made  search  for  their  resting-place,  and  finally 
detected  an  area  about  as  large  as  an  half-crown  piece,  just  external 
to  and  below  the  right  nipple,  where  there  was  harsh  breathing  and 
an  occasional  rale ;  lung  puncture  was  resorted  to,  2  c.c.  of  broth 
introduced  into  the  lung  tissues  and  part  of  it  aspirated  away  again. 
From  this  fluid  pure  cultures  of  the  pneumococcus  and  B.  influenzcE  were 
obtained,  and  vaccines  of  these  made  and  utilised  in  treatment.  It  is 
yet  too  soon  to  be  certain  of  the  ultimate  effect  as  only  about  a  year 
have  elapsed  since  treatment  was  begun,  but  Dr.  Brookhouse  has 
recently  informed  me  that  so  far  there  has  been  no  recurrence. 

Another  case  was  that  of  an  old  man,  aged  84  years,  very  hale  and 
hearty,  but  the  victim  to  every  catarrhal  epidemic  which  arose.  These 
always  led  to  a  fortnight's  confinement  to  bed  and  a  further  month  of 
convalescence.  I  was  called  in  to  see  him  three  years  ago,  and  found 
the  chief  invader  to  be  the  pneumococcus,  the  M.  catarrhalis  being  also 
present.  I  made  vaccines  and  gave  him  an  inoculation  of  50  millions 
of  each,  with  the  result  that  he  was  out  walking  in  the  sunshine  upon 
the  third  day.  Treatment  was  continued  for  six  months,  as  careful 
examinations  of  the  scanty  sputum  shewed  the  continued  presence  of 
the  pneumococcus.  The  patient  then  went  to  Biarritz,  where  Sir 
James  Reid  kindly  continued  the  inoculations  for  me.  When  the 
patient  returned  two  months  later,  he  was  very  well  indeed,  but  in  the 
lump  of  sputum  which  he  voided  daily  on  waking,  pneumococci  still 
were  present.  Treatment  was  continued  at  intervals  of  about  four 
months,  the  result  being  that  in  all  the  three  years  the  patient  has 
completely  escaped  every  catarrhal  epidemic,  despite  his  advanced 
years,  and  the  fact  that  he  now  winters  each  year  in   England  till  the 


1 86  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

middle  of  February.  When  last  I  saw  him  the  pneumococci  still  were 
present,  and  I  strongly  urged  upon  the  patient  the  necessity  of 
continuing  with  periodic  inoculations.  I  told  him  that  it  was  only  by 
persistent  treatment  at  eight-  to  ten-day  intervals  that  a  reasonable 
expectation  of  freeing  him  from  his  enemies  could  be  held,  and  that  as 
this  was  hardly  practicable  the  only  alternative  was  to  maintain  his 
resistance  at  a  high  level  by  occasional  inoculations. 

I  could  cite  several  other  cases  to  illustrate  this  point,  but  these 
two  must  perforce  suffice. 

The  importance  of  this  observation  in  the  treatment  of  a  patient 
who  contracts  an  influenza-pneumococcal  cold  is  obvious ;  vaccine 
treatment  must  be  continued  at  regular  intervals  until  repeated 
bacteriological  examinations  have  revealed  the  complete  rout  of  the 
invaders,  or  if  this  cannot  be  secured — and  this  unfortunately  will 
surely  prove  to  be  so  in  a  certain  proportion  of  cases — a  short  series  of 
inoculations  at  intervals,  say^  of  three  or  four  months,  must  on  no 
account  be  omitted ;  in  this  way  acute  exacerbations  may  be  obviated. 

The  favourable  experiences  which  have  resulted  in  my  hands  from 
the  use  of  the  measures  described  in  this  section  have  been  corroborated 
to  a  certain  extent  by  those  of  others.  Thus  Webb  in  Kleb's  Tuberculosis, 
p.  590,  says  :• 

"  At  the  time  of  writing  45  patients  undergoing  inoculation  with 
tuberculin  and  mixed  vaccines  have  been  exposed  to  a  very  wide-spread 
epidemic  of  a  catarrhal  condition,  due  chiefly  to  the  B.  influenzce, 
partly  to  M.  catarrhalis.  Of  these  45  patients,  5  had  the  influenza 
bacillus  persistently  in  the  sputa,  and  they  have  been  inoculated 
periodically  with  their  influenza  vaccine.  These  have  escaped  colds, 
The  results  are  only  suggestive ;  they  may  be  tabulated  as  follows : 

Particulars.  No.  Result. 

"  Inoculated  against  influenza  with  their 

own  vaccine.  5         Escaped  epidemic. 

"  Inoculated   against   influenza    with    a 

stock  vaccine.  8  „ 

"  (All    these  gave   accurate  histories   of 

repeated  former  attacks.) 
"  Preventive     inoculations     not     given, 

patients  denying  that  they   ever   had 

influenza.  32  15  contracted  colds  and 

died. 

"  In  the  sputa  of  all  15  who  died  the  B.  infiuenzcB  was  found  :  two  of 
these  for  the  first  time  developed  very  serious  haemorrhages  within  a 
few  days  of  the  infection." 

He  states  that  he  has  observed  a  patient's  opsonic  index  to   the 


THE    BACTERIAL    DISEASES    OE    RESPIRATION.  I  87 

tubercle  bacillus  lowered  to  0'6  during  an  influenzal  attack  and 
continues : 

"  It  is  a  common  observation  that  patients  with  pulmonary  tuber- 
culosis mav  go  rapidlv  down  hill  following  an  attack  of  influenza,  and 
the  writer  would  suggest  that  the  prevention  of  such  concomitant 
infection  should  be  sought  by  the  means  indicated  above." 

On  page  599  he  says — "  A  lasting  immunity  must  not  be  expected 
from  inoculations  by  these  vaccines,  just  as  a  lasting  immunity  to  the 
tubercle  bacillus  is  unattainable  by  any  tuberculin  administration. 
After  the  apparent  maximum  results  have  been  obtained  most  patients 
have  been  kept  in  touch  by  inoculation  at  intervals  of  a  few  weeks."' 

Powell  and  Hartley  (Diseases  of  the  Lungs,  p.  514),  say:  "In  some 
cases  in  which  there  is  an  inveterate  tendency  to  recurrent  catarrh, 
whether  influenzal  or  otherwise,  it  may  be  thought  desirable  to  ascertain 
the  organism  of  infection — }I.  catarrhalis,  B.  coryzcB  segnientosus,  B. 
influenza:,  the  pneumococcus  or  other — and  to  prepare  a  vaccine  to  be 
used  at  appropriate  intervals,  with  a  view  to  increase  the  resistance 
to  these  organisms,  and  thus  ward  off  the  attack." 

Methods    other    than    Specific    employed    in    the    Prevention    and   Cure    of 

Concomitant  Infections. 

Of  the  methods  other  than  specific  which  are  available  for  the 
prevention  of  mixed  infections  in  phthisis,  not  much  remains  for 
mention;  they  may  all  be  included  in  the  phrase  "the  general 
hygiene  of  the  bodv."  More  and  more  is  it  forced  upon  our  notice 
that  bacterial  invasions  depend  upon  a  lowering  of  the  general  vitality 
of  the  tissues,  for  upon  their  vitality  the  formation  of  sufficient  anti- 
bodies in  part  depends.  Manv  members  of  the  community  appear  to  be 
peculiarly  susceptible  to  the  attacks  of  one  or  more  bacterial  enemies, 
and,  as  has  been  amply  demonstrated  during  the  past  few  years, 
therapeutic  immunisation  with  the  corresponding  bacterial  emulsions 
will  do  much  to  render  them  immune.  Unfortunately  this  procedure, 
admirable  as  are  the  results  it  frequently  secures,  sometimes  fails,  and 
this  failure  is  due  to  the  following  defect  in  the  method :  it  does  little 
or  even  nothing  to  remedy  permanently  the  ingrained  and  perhaps 
congenital  defect  on  the  part  of  the  tissues  in  the  elaboration  of  the 
specific  antibodies.  It  supplies  a  stimulus,  but  the  effect  of  all  stimuli 
wears  off  in  course  of  time  unless  a  constant  vis  a  tergo  is  maintained : 
constant  stimulation  may  perhaps  train  the  tissues  in  the  way  in  which 
they  should  go,  but  given  an  inherent  weakness  on  their  part  to  make 
response  beyond  a  certain  point,  and  constant  stimulation  can  only  end 
in  exhaustion  more  or  less  complete. 


1 88  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

Herein  lies  the  danger  in  all  forms  of  specific  therapy,  and  this 
danger  can  only  be  avoided  by  the  simultaneous  removal,  more  or  less 
complete,  of  the  intrinsic  defect  in  the  tissues.  Our  ignorance  of  the 
minute  mechanisms  of  the  body  and  of  the  precise  factors  concerned  in 
the  maintenance  of  immunity  are  serious-  obstacles  to  the  securing  of 
the  desired  result.  Clinical  experience,  however,  clearly  indicates 
that  a  healthy  condition  of  the  tissues  is  only  to  be  maintained  by  the 
strict  adherence  to  certain  laws  of  hygiene.  These  are  so  well  known 
and  so  fully  described  in  all  treatises  upon  the  diseases  of  the  chest 
that  there  is  little  need  for  my  dwelling  on  them  here.  I  have  already 
emphasised  the  necessity  of  dealing  with  all  infective  foci  in  the 
body  generally,  and  so  of  removing  all  sources  of  toxic  absorption 
which  impair  the  general  nutrition  and  the  resisting  powers  of  the 
tissues  devoted  to  the  elaboration  of  the  immune  bodies,  and  of 
securing  proper  freedom  of  the  air-passages  and  of  inculcating  correct 
methods  of  respiration.  A  pure  and  adequate  supply  of  air  must  be 
ensured,  proper  food  in  adequate  amounts  must  be  supplied,  and  its 
utilisation  made  possible  by  attention  to  the  organs  of  mastication,  to 
the  stomach  and  the  bowels.  If  necessary  the  appetite  must  be  stimu- 
lated by  the  use  of  suitable  tonics.  Mental  quietude  is  a  desideratum 
for  all,  and  suitable  exercise  an  important  essential.  Finally  isolation 
as  far  as  possible  of  all  those  who  suffer  from  infectious  diseases,  and 
into  this  category  catarrhal  attacks  most  certainly  fall,  and  their 
adequate  treatment  cannot  fail  to  remove  an  important  potential  source 
of  danger  to  others. 

These  are  the  general  prophylactic  methods  whereby  the  incidence 
of  mixed  infection  may  be  diminished  in  the  phthisical.  It  remains 
to  consider  the  methods  other  than  specific  which  may  be  utilised  in 
the  treatment  of  mixed  infection  when  it  has  already  supervened. 

Absolute  rest  in  bed  until  the  pyrexia  is  under  control  and  open-air 
lines  of  treatment  cannot  be  too  strictly  enforced  ;  an  abundant  and 
well-assorted  dietary  rich  in  fats  and  nitrogenous  elements  and  con- 
ducive to  their  retention  in  the  body  is  essential ;  plenty  of  good  milk 
and  cod-liver  oil  with  the  addition  perhaps  of  a  little  strychnia,  iron 
or  arsenic  being  included  if  possible ;  while  various  forms  of  drug 
treatment  have  been  devised  for  dealing  with  the  mixed  infection. 
These  comprise  :  (i)  antiseptic  inhalations  ;  (2)  intra-tracheal  injections; 
(3)  drugs  by  the  mouth ;  (4)  subcutaneous  and  intra-venous  inocula- 
tions ;  (5)   applications  from  without ;  and  will  be  considered  in  order. 

To  Dr.  Churchill  may  be  justly  attributed  not  only  the  intro- 
duction of  hypophosphites  in  the  treatment  of  pulmonary  tuber- 
culosis, but  also  of  inhalant  mixtures  for  the  combat  of  mixed  infections. 
His  so-called  spirone  was  a  mixture   of  iodine,  potassium  hyposulphite 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  I  S9 

and  acetone,  and  was  much  belauded  by  its  inventor ;  recent  analyses 
performed  at  the  Lister  Institute  and  Clinical  Research  laboratories 
tend  to  show  that  it  is  practically  devoid  of  antiseptic  properties,  con- 
taining onlv  a  solution  of  potassium  iodide  and  potassium  tetrathionate 
in  acetone. 

The  use  of  inhalations  passed  somewhat  out  of  vogue,  but  has  been 
continued  by  Drs.  Burney  Yeo,  David  Lees,  Muthu  and  others,  and 
its  proper  importance  been  assigned  to  it.  The  absolute  necessity 
of  continuous  inhalation,  not  of  one  extending  over  merely  a  few 
hours  daily,  has  been  demonstrated.  As  the  treatment  is  apt  to 
prove  irksome  to  the  patient  the  use  of  specially  light  but  well-fitting 
respirators  is  very  advisable.  Messrs.  Maw  and  Sons  manufacture  a  form 
devised  bv  Dr.  Burney  Yeo  consisting  of  perforated  zinc  bound  round 
the  edge  with  chamois  leather,  and  furnished  with  a  small  receptacle 
for  the  cotton-wool  to  which  the  respiratory  mixture  is  added. 

Various  mixtures  for  inhalation  have  been  devised ;  the  one  most 
in  use  at  Brompton  Hospital  is  one  composed  of  equal  parts  of  tincture 
of  iodine,  liquefied  carbolic  acid,  creosote,  ether  and  rectified  spirit ; 
another  is  menthol  5ij,  creosote  5iss,  spiritus  camphorse  3iss,  spiritum 
rectificatum  ad  5J.  Twenty  drops  of  either  of  these  are  to  be  employed 
hourly  to  moisten  the  cotton-wool  inside  the  respirator. 

Some  mixtures  suit  certain  patients  better  than  others  :  for  instance 
when  the  larynx  is  involved  one  containing  menthol  seems  to  give  the 
best  results,  when  there  is  troublesome  laryngeal  cough  the  addition  of 
chloroform  appears  to  be  indicated,  while  the  addition  of  3J  of  oil  of 
bitter  almonds  to  an  ounce  of  mixture  seems  of  especial  service  to 
some.     If  one  mixture  does  not  suit,  trial  should  be  made  of  another. 

Personally  I  have  been  disposed  to  regard  antiseptic  inhalations  as 
having  little  direct  influence  upon  the  mixed  infections  of  phthisis,  and 
to  attribute  their  undoubted  good  effects  to  the  diminution  of  cough  and 
the  increased  comfort  of  the  patient.  Others  whose  experience  is  far 
greater  than  my  own  insist  upon  their  sterilising  action ;  among  these 
I  may  mention  Dr.  David  Lees  and  Dr.  Burney  Yeo. 

Intra-tracheal  injections. — Intra-tracheal  injections  have  found  espe- 
cial favour  abroad,  and  have  been  advocated  in  this  country  by  Sir 
T.  Grainger  Stewart,  Mr.  Colin  Campbell  and  others.  By  means  of  a 
special  form  of  syringe  and  a  certain  amount  of  practice  these  may  be 
made  wnth  little  inconvenience  to  the  patient.  A  drachm  or  two  of 
one  of  the  following  mixtures  should  be  injected  once  or  twice  daily  : 
menthol  10  parts ;  guaiacol  2  parts;  olive  oil  88  parts,  or  gomenol  5-10 
parts,  olive  oil  to  100  parts.  Suspensions  of  iodoform  in  olive  oil 
have  been  similarly  employed.  This  method  of  treatment  appears  to 
be  of  especial  service  in  cases  of  advanced  cavitation,   but   the   results 


I90  THE    BACTERIAL    DISEASES    OE    RESPIRATION. 

obtained  var}^  greatly  from  almost  complete  failure  to  a  considerable 
measure  of  success. 

Drugs  by  the  mouth. — The  drug  treatment  by  the  mouth  of  the 
mixed  infections  of  pulmonary  tuberculosis  can  hardly  be  anticipated 
to  produce  any  marked  bactericidal  or  inhibitory  effect  unless  persisted 
in  for  a  considerable  period.  It  has  also  the  additional  disadvantage 
that  it  may  tend  to  upset  the  digestive  apparatus.  Drugs  by  the 
mouth  also  require  to  be  employed  with  considerable  discretion  :  a 
preparation  well  suited  for  use  in  one  class  of  case  may  be  inadvisable 
in  another  class  of  case.  For  instance,  when  there  is  little  or  no 
pyrexia  but  considerable  expectoration,  the  preparations  of  tar,  creosote 
or  eucalyptus  in  moderate  doses  may  prove  of  service.  The  tar  or 
creosote  may  be  given  as  a  pill,  five  or  ten  drops  of  eucalyptus  oil  and 
terebene  in  equal  parts  may  be  taken  on  sugar,  while  tar  is  best  given  as 
a  morning  and  evening  dose  of  eau  de  goudron,  5j,  in  a  little  warm  milk  to 
which  a  teaspoonful  of  brandy  may  be  added.  Creosote  and  guaiacol 
may  be  given  in  2  to  4  ni  doses  inside  a  perle  or  capsule.  These 
preparations  all  act  through  their  excretion  by  the  bronchial  mucous 
membrane,  whereby  suppurative  processes  in  the  walls  of  cavities  and 
around  tuberculous  foci  is  limited.  When  it  is  remembered  that 
suppuration  is  an  important  means  whereby  necrotic  tuberculous  tissue 
is  eliminated,  explanation  is  afforded  of  the  clinical  fact  that  remedies 
of  the  creosote  class  prove  of  very  doubtful  service  during  the  acute 
and  actively  pyrexial  stages  of  phthisis,  and  are  especially  indicated  as 
the  pyrexia  is  subsiding  and  the  more  quiescent  period  entered  on. 

In  the  former  stage,  therefore,  the  object  of  drug  treatment  is  rather 
to  be  directed  towards  the  limitation  of  toxic  absorption  by  the  control  of 
excessive  coughing  and  the  promotion  of  easy  expectoration  rather  than 
to  the  limitation  of  the  sputum. 

In  the  chronic  fibroid  stage  drugs  may  be  employed  with  greater 
freedom  according  to  the  nature  of  the  cough  and  the  amount  of  the 
expectoration. 

Subcutaneous  and  intra-venous  inoculations. — The  subcutaneous  and 
intravenous  introduction  of  antiseptic  drugs  with  the  object  of  a 
"sterilisans  magna"  has  been  repeatedly  advocated.  Numerous  drugs 
such  as  formalin,  iodoform,  mercury  succinimide,  quinine  derivatives, 
creosote  and  guaiacol  either  as  aqueous  solutions  or  as  oily  suspensions 
have  been  employed,  and  beneficial  results  recorded.  The  destruction 
of  the  tubercle  bacilli  in  situ  has  been  the  object  aimed  at ;  this,  it  may 
at  once  be  said,  is  an  absolute  impossibility :  for  the  destruction  of  the 
tubercle  bacilli  such  a  dose  of  antiseptic  would  have  to  be  given  as 
would  necessarily  hasten  considerably  the  patient's  end.  It  is  hardly 
even  likely  that  the  death  of  the  much  more  easily  destructible  secondary 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  191 

invaders  has  been  accomplished.  Such  a  lowering  in  their  vitality 
may,  however,  have  been  produced  as  would  enable  the  tissues  of  the 
lung  the  better  to  grapple  with  their  enemies.  The  discovery  by 
Ehrlich  and  Hata  of  drugs  which  have  a  selective  action,  combining  with 
certain  protoplasm  but  not  with  others,  affords  hope  that  the  discovery 
may  yet  be  made  of  drugs  which  have  a  special  affinity  for  the  tubercle 
bacillus,  pneumococcus,  B.  influenzcs,  etc.  Morgenroth  claims  to  have 
found  such  an  one  for  the  pneumococcus  in  a  certain  complex  quinine 
derivative.  Sir  Almroth  Wright  confirms  its  selective  action  and  has 
found  that  it  will  destroy  pneumococci  in  the  blood-stream ;  its  prac- 
tical utility  in  cases  of  pneumonia  he  has  disproved,  and  it  is  hardly 
advisable  to  be  unduly  optimistic  of  success  by  any  method  of  "  sterili- 
sans  magna.'' 

Regarding  the  use  of  intra-muscular  injections  of  creosote  or  guaiacol 
dissolved  in  olive  oil,  Powell  and  Hartley  say :  "  We  have  had  oppor- 
tunities of  noticing  the  results  of  this  method  of  treatment,  but  have  by 
no  means  been  convinced  of  its  superiority  (/.  e.  to  mouth  medication)  ; 
the  imagination  of  the  patient  cannot  fail  for  a  time  to  be  impressed, 
but  at  the  cost  of  considerable  discomfort  and  in  some  instances  of  no 
little  positive  suffering,  local  necrosis  sometimes  occurring  at  the  seat 
of  injection." 

Applications  from  without. — The  application  of  strong  iodine  pre- 
parations or  of  blisters,  while  yet  useful  in  the  treatment  of  quiescent 
cavities,  can  hardly  be  expected  to  produce  any  direct  influence  upon  the 
secondary  infection. 

The  utility  of  radium  applications  in  the  treatment  of  bacterial 
diseases  has  been  so  much  to  the  front  of  late  that  the  question  at  once 
occurs  whether  they  would  prove  of  any  avail  in  the  treatment  of  the 
condition  with  which,  we  are  concerned.  No  authoritative  and  authentic 
statements  on  this  point  have  yet  occurred  in  print.  I  have,  however, 
heard  privately  that  a  radium  corset  has  been  devised  completely 
enveloping  the  chest,  and  that  the  application  of  this  for  one  hour  daily 
has  been  productive  of  some  good  results.  Further  information 
uiion  this  subject  will  be  awaited  with  much  interest,  but  the  method 
obviously  can  hardly  become  one  of  general  applicability. 


CHAPTER    XI. 

INFECTIONS  BY  THE  TUBERCLE  BACILLUS  AND  THE 
USE  OF  SPECIFIC  PRODUCTS  IN  THEIR  TREAT- 
MENT. 

In  the  preceding  chapter  I  have  endeavoured  to  bring  before  the 
reader  the  paramount  importance  of  mixed  mfection  in  many,  if  not 
most,  cases  of  pulmonary  tuberculosis,  and  the  necessity  of  coping 
adequately  with  these  allied  invaders  before  endeavouring  to  secure 
the  extinction  of  the  infection  by  the  B.  tuberculosis  itself.  It  now 
remains  to  consider  how  this  latter  objective  may  be  attained,  and  this 
question  I  propose  to  discuss  according  to  the  following  scheme  : 

(i)  The  tubercle  bacillus  group.  Its  distribution  in  nature — paths 
of  infection-^constitution  of  the  bacillus,  its  toxins,  and  their  actions 
on  the  tissues.  The  defensive  mechanism  of  the  body  and  how  this 
may  be  assisted  generally. 

(2)  The  tuberculins  and  their  use  in  the  diagnosis  of  pulmonary 
tuberculosis.  "  Allergie  "  or  reactivity — cutaneous  test  of  Von  Pirquet 
— percutaneous  test  of  Morro — Carle  Woodcock  blister  test — intra- 
dermal test — ophthalmo  test  of  Wolff  Eisner  and  Calmette — the  sub- 
cutaneous test — opsonic  index  estimations. 

(3)  Classification  of  cases  of  pulmonary  tuberculosis  according  to 
{a)  extent  and  nature  of  lesions,  (6)  auto-inoculatory  phenomena — the 
nature  of  the  immunity  that  can  be  secured  by  means  of  tuberculin — 
selection  of  cases  for  specific  therapy. 

(4)  Choice  of  tuberculin — conduct  of  course  of  treatment — control 
of  dosage  and  intervals. 

(5)  Treatment  by  the  induction  and  control  of  auto-inoculations. 

(6)  Results. 

The  Tubercle  Bacillus  Group — Its  Distribution  in  Nature — Paths  of  In- 
fection in  Man — The  Constituents  of  the  Bacillus,  its  Toxins,  and  'their 
Actions  on  the  Tissues. 

As  we  have  seen  on  p.  ig,  the  B.  tuberculosis  belongs  to  the  group  of 
bacilli  known   as  acid-fast,  which   also  includes  the  smegma  bacillus, 


THE    BACTERIAL    DISEASES    OE    RESPIRATION.  1 93 

B.  leprcB,  B.phlei,  or  Timothy  grass  bacillus,  the  Mycobacterium  lacticola, 
or  butter  bacillus  of  Rabinowitsch,  and  other  little-known  organisms. 
These  are  now  regarded  as  being  more  correctly  designated  as  m^'co- 
bacteria.  or  even  as  streptothrices. 

While  it  is  true  that  the  B.  phlei  and  Mycobacterium  lacticola  grow 
readily  at  a  temperature  of  22°  C,  this  fact,  contrary  to  the  usual 
statem.ent,  does  not  suffice  to  differentiate  them  from  all  varieties  of 
the  B.  tuberculosis,  for  it  is  now  known  that  such  cold-blooded  animals 
as  the  tortoise,  frog,  blindworm  and  fishes  are  sometimes  infected  by 
varieties  of  the  bacillus,  morphologically  closely  resembling  the 
varieties  which  infect  the  warm-blooded  animals.  Man,  cattle,  swine, 
horses,  monkeys,  rabbits,  guinea-pigs,  dogs,  cats,  birds,  and,  in  fact, 
most  w'arm-blooded  animals,  are  susceptible  to  the  attacks  of  the  B. 
ttcberculosis,  and  considerable  investigation  has  been  conducted  upon 
the  identity  or  otherwise  of  the  several  varieties  of  the  bacillus.  The 
discussion  has  waxed  exceedingly  hot  in  regard  to  the  human  and 
bovine  bacilli,  but  the  consensus  of  opinion  now  is  that  the  two  are 
distinct  varieties,  and  are  not  convertible  the  one  into  the  other  by 
even  very  prolonged  residence  in  the  tissues  of  the  alien  host. 

In  each  species  pathological  conditions  can  be  initiated  b}'  the 
introduction  into  suitable  sites  in  its  tissues  of  living  bacteria  derived 
from  the  other  animal,  but  man  is  more  susceptible  to  the  attacks  of 
the  bovine  bacillus  than  are  cattle  to  the  attacks  of  the  human  bacillus. 
Indeed,  Behring  and  Baumgarten  have  shown  that  under  certain  condi- 
tions cattle  can  be  rendered  immune  to  the  bovine  bacillus  by  means 
of  inoculations  with  living  cultures  of  the  human  strain.  As  we 
shall  see  later,  Spengler,  Klemperer,  Klimmer,  and  Friedmann  have 
attempted  to  bring  about  an  analogous  result  in  man  wath  bacilli 
derived  from  various  sources,  but  with  doubtful  success.  The  question 
of  the  infection  of  man  b}-  the  bo\'ine  bacillus  is  one  of  immense 
economic  importance,  and  has  great  bearing  upon  the  means  whereby 
tuberculosis  is  initiated  in  the  human  subject.  It  is  quite  impossible 
here  to  enter  into  a  lengthv  discussion  of  the  various  differences  of 
observation  and  of  opinion  :  as  regards  the  following  points  there  is 
almost  general  agreement : 

(a)  That  tuberculosis  in  man  can  be  initiated  both  by  the  human 
and  bovine  strains,  despite  the  failures  on  the  part  of  Spengler  and  of 
Klemperer  to  infect  themselves  bv  subcutaneous  inoculation  with  h-gr. 
doses  of  living  virulent  bovine  bacilli. 

(b)  That  there  is  no  very  marked  difference  between  the  incidence 
rate  of  tuberculosis  in  countries  w'here  cow's  milk  is  freely  consumed, 
and  that  in  countries  where  it  is  not  used  for  human  consumption. 

(c)  That  there  is,  however,  a  certain  difference  in  the  nature  of  the 

13 


194  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

tuberculous  lesions  initiated  by  the  two  bacilli,  glandular  tubercu- 
losis, especially  in  the  abdomen  and  less  frequently  in  the  neck,  being 
especially  common  in  those  countries  where  cow's  milk  is  freely  con- 
sumed. Bacteriological  examinations  have  confirmed  the  frequency  of 
bovine  infection  of  the  glandular  system  in  man.  Only  occasionally 
are  the  bones,  joints,  or  meninges  attacked  by  the  bovine  bacillus,  and 
very  rarely  the  pulmonary  tissues.  Carl  Spengler  has  modified  his 
origmal  view^  that  in  pulmonary  tuberculosis  the  two  bacilli  occur  side 
by  side,  and  now  states  that  two  t3^pes,  which  he  calls  human  and 
bovo-human,  so  occur,  and  that  the  latter  type  is  identical  with  Aluch's 
granular  non-acid-fast  variety. 

Paths  of  Infection. 

Assuming,  then,  that  pulmonary  tuberculosis  is  almost  always 
spread  from  man  to  man — though  personally  I  believe  that  insufficient 
attention  is  paid  to  the  domestic  cat  as  the  carrier  of  infection  to  the 
children  who  pet  and  fondle  them — it  is  necessary  to  consider  briefly 
the  routes  whereby  the  bacilli  may  reach  the  lungs.  Among  these  may 
be  mentioned  : 

(fl)    Via  the  placental  circulation — this  is  certainly  very  rare. 

{b)  Via  the  maternal  milk — a  possibility  which  has  not,  I  feel, 
received  sufficient  consideration,  for  if  tubercle  bacilli  are  freely  dis- 
charged in  the  milk  of  tuberculous  cows,  whose  udders,  nevertheless, 
are  perfectly  healthy,  it  is  almost  inconceivable  that  bacilli  are  not  like- 
wise excreted  in  the  milk  of  tuberculous  mothers. 

(c)  By  the  transference  of  the  bacilli  to  the  mouth  from  the  hands 
of  children  crawling  about  the  floor  of  rooms  frequented  by  a  tubercu- 
lous person. 

{d)  Transference  of  the  bacilli  to  the  lips  in  the  act  of  kissing,  a 
danger  which  is  greatly  increased  if  a  tuberculous  male  be  allowed  to 
retain  a  beard  or  moustache. 

{e)  By  inhalation  into  the  upper  respiratory  tract  of  air  laden  with 
tubercle  bacilli,  which  may  be — 

(i)  Caught  up  by  the  nasal  mucosa,  and  be  either  destroyed  there 
by  the  endothelial  and  lymphoid  cells,  or  be  swallowed  in  the  excessive 
secretion  of  a  nasal  or  post-nasal  catarrh,  or  be  expelled  upon  the 
handkerchief. 

(2)  Caught  up  by  the  saliva  and  swallowed,  or  they  may  find  a 
portal  of  entry  into  the  tonsils  or  adenoid  tissue  of  the  naso-pharynx. 

(3)  Entangled  by  the  ciliated  cells  of  the  larynx  and  trachea  and 
find  lodgment  there  or  be  expectorated  in  the  sputum. 

(4)  Carried  down  into  the  bronchi  and  bronchioles  with  the 
respiratory  air  and  deposited  in  the  pulmonary  tissues. 


THE    BACTERIAL    DISEASES    OE    RESPIRATION.  1 95 

Whatever  the  portal  of  entry  may  be  the  bacilH  may  enter  the 
lymphatic  spaces,  and  possibh"  the  blood-vessels  ;  in  the  former  event 
the}'  are  carried  to  the  nearest  lymph-node,  where  either  they  ma}'  be 
detained,  or  thev  mav  be  allowed  to  pass  through  and  even  enter 
ultimatelv  the  general  blood-stream.  Thus,  bacilli  of  the  human  type 
mav  be  air-borne,  and  yet  the  foci  of  infection  may  be  established  in 
such  diverse  situations  as  the  nose,  tonsils,  adenoid  tissue  of  the  naso- 
pharynx, cervical  glands,  larynx,  bronchial  glands,  pulmonary  tissues, 
or  abdominal  glands. 

Bovine  bacilli  are  commonh-  ingested  in  infected  milk,  and  either 
adhere  to  the  mucous  membrane  of  the  pharynx  and  enter  the  tonsils 
and  cervical  glands,  or  are  absorbed  through  the  permeable  mucous 
membrane  of  the  gastro-intestinal  tract  and  infect  the  abdominal 
glands  and  peritoneum,  but  only  rareh"  the  pulmonary  tissues. 

The  Constitution  of  the  Tubercle  Bacillus;   its  Toxins  and  their  Actions 

upon  the  Tissues. 

The  tubercle  bacillus  can  be  readily  grown  under  artificial  con- 
ditions, although  its  rate  of  multiplication  is  slow  relative  to  most 
other  micro-organisms.  The  best  media  for  the  purpose  are :  solid 
media,  Dorset's  egg  medium  or  glycerine  agar,  liquid  medium,  veal 
broth  containing  5  per  cent,  ghxerine.  If  the  bacteria  be  scraped  off 
the  surface  of  the  solid  medium  and  be  extracted  with  various  solvents 
certain  bodies  are  obtained  :  among  these  may  be  mentioned  : 

d)  A  fattv  acid,  which  confers  upon  the  bacillus  its  acid-fast 
character  and  appears  to  have  more  or  less  the  same  constitution  in  all 
acid-fast  bacteria.  This  body  is  said  to  be  the  cause  of  the  chronic 
inflammatory  and  caseous  changes  which  occur  in  the  tissues. 

(2)  Albumoses  which  are  capable  of  causing  rise  of  temperature 
when  injected  into  the  tissues,  and  are  probably  responsible  for  some 
of  the  pvrexial  svmptoms  in  the  natural  course  of  the  disease. 

(3)  Certain  volatile  bodies  which  are  said  to  have  a  convulsant 
action. 

Renon  gives  the  following  account  of  the  products  which  may  be 
obtained  with  various  solvents  : 

(i)   Distilled  water  removes  albumins. 

(2)  A  10  per  cent,  solution  of  sodium  chloride  acting  for  twenty- 
four  hours  at  38°  C.  removes  globulins. 

(3)  Alcohol;  ether,  and  chloroform  remove  the  fatty  envelope,  the 
two  former  more  especially  that  constituent  which  leads  to  caseation 
effects,  the  chloroform  the  body  which  induces  sclerosis. 

(4)  Strong  acetic  acid  at  So"  C.  dissolves  the  casein,  a  para-nucleo 


196  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

albumin,  which  is  the  essential  protoplasmic  substance,  and  which 
when  stained  with  carbol  fuchsin  strongly  resists  decolorisation  by 
means  of  acid,  but  yields  more  readily  to  treatment  with  absolute 
alcohol. 

There  is  thus  no  doubt  that  the  tubercle  bacillus  forms  within 
itself  bodies  capable  of  producing  definite  pathological  effects  upon  the 
tissues  of  its  host,  and  known  as  intra-cellular  or  endo-toxins.  These 
are  not  set  free  until  the  death  of  the  bacillus  and  its  subsequent 
disintegration  or  solution. 

Whether  the  bacillus  also  resembles  the  B.  diphtherice  in  forming 
poisonous  substances  which  are  excreted  "in  vivo''  into  the  tissues  of  the 
host  is  not  certain  ;  probably  a  minute  quantity  of  extra-cellular  or 
exo-toxin  is  so  formed,  but  the  rate  of  multiplication  of  the  bacillus  in 
artificial  culture  is  so  slow  that  it  is  very  difficult  to  determine  with 
certainty  whether  the  whole  of  the  toxin  found  in  the  culture  fluid  is 
not  simply  endo-toxin  set  free  by  the  death  and  autolysis  of  the  bacilli. 
However  this  may  be,  it  is  certain  that  the  role  played  by  any  exo- 
toxin is  of  negligible  importance  compared  with  that  played  by  the 
endo-toxins. 

The  Defensive  Mechanism  of  the  Body  against  the  Tubercle  Bacillus,  and 
how  this  may  be  assisted  generally. 

The  defensive  mechanism  of  the  body  against  the  tubercle  bacillus 
is  but  little  understood.  In  the  case  of  certain  acute  infective  disorders 
such  as  scarlet  fever,  measles,  and  smallpox,  one  attack  seems  to 
confer  a  very  high  degree  of  active  immunity  which  may  even  last  a 
lifetime,  and  it  is  accordingly  rare  for  the  individual  to  be  subjected  to 
a  second  attack.  Such  does  not  appear  to  be  the  case  with  tuberculosis  ; 
so  far  from  one  attack  conferring  immunity  against  a  second  it  seems 
rather  to  predispose  to  it  ;  that  is,  if  we  except  the  immunity  to 
subsequent  infection  by  the  human  strain  which  may  possibly  be 
conferred  by  an  infection  due  to  the  bovine  type.  Koch  thought  that 
he  detected  some  attempt  at  the  establishment  of  immunity  in  cases  of 
miliary  tuberculosis,  but  inasmuch  as  these  cases  always  end  fatally, 
the  attempt  obviously  is  doomed  to  failure.  At  the  same  time,  if  an 
animal  deeply  infected  intra-abdominally  with  tuberculosis  be  inoculated 
subcutaneously  with  virulent  bacilli,  a  slight  lesion  which  rapidly  heals 
is  the  sole  result. 

That  general  constitutional  immunity  exists,  due  probably  to 
bio-chemical  causes,  is  highly  likely,  but  local  immunity  appears  to  be 
a  most  important  defensive  mechanism,  as  is  well  shown  by  the  fact 
that  areas  of  advance  and  of  cure  may  occur  simultaneously,  not  only 
in  the  same  patient,  but  also  in  different  parts  of  the  same  lesion,  as  is 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  1 97 

often  seen  in  cases  of  lupus  and  of  tuberculosis  of  the  synovial  mem- 
branes. Limitation  of  local  processes  is  brought  about  by  the 
organisation  of  the  giant-cell  systems  and  the  formation  of  fibrous 
tissue  and  by  the  calcification  of  caseous  areas. 

Phagocytosis,  apparently,  is  a  very  important  agency  in  the  destruc- 
tion of  the  bacilli,  and  is  performed  mainly  by  the  giant  and  endothelial 
cells  and  by  the  lymphocytes ;  the  polymorphonuclear  leucocytes  are 
possibly  of  service  in  destroying  such  bacilli  as  may  gain  access  to 
the  blood-stream,  but  inasmuch  as  the  ingress  of  any  considerable 
numbers  of  bacilli  into  the  circulation  almost  invariably  leads  to 
generalised  tuberculosis,  they  obviously  fail  to  fulfil  this  role  completely. 
That  the  amount  of  opsonin  in  the  circulating  fluids  is  of  consider- 
able moment  to  the  activities  of  the  polymorphonuclear  leucocytes  has 
been  amply  demonstrated,  but  whether  opsonin  is  of  any  service  in 
assisting  the  giant  and  endothelial  cells  in  the  performance  of  phago- 
cytosis is  not  known.  It  is  probable  that  the  toxic  products  formed  by 
the  bacilli  stimulate  these  cells  to  proliferate  and  so  to  grow  round  and 
enclose  the  invaders. 

A gglutinin  for  the  tubercle  bacillus  is  sometimes  found  to  be  present 
in  the  serum  of  infected  individuals  in  considerable  quantities  ;  in  the 
healthy  it  is  altogether  absent,  or  present  only  to  a  negligible  degree. 
Inasmuch  as  it  may  be  almost  altogether  absent  throughout  the  course 
of  an  attack,  and  yet  progress  to  recovery  be  quite  satisfactory,  the 
importance  of  agglutinin  in  immunity  cannot  be  very  great. 

Formation  of  hactericidin  and  of  antitoxin  has  not  been  satisfactorily 
demonstrated,  nevertheless  some  formation  of  the  latter  almost 
certainly  occurs.  As  we  shall  see  later,  the  tissue-cells  respond  to  in- 
creasing doses  of  toxins,  not  by  the  elaboration  of  antitoxin,  but  by 
acquiring  tolerance  of  the  poison.  On  the  other  hand  the  importance 
of  lysin  is  becoming  increasingly  clearer  :  whereas  the  amount  of 
tuberculo-lysin  in  the  tissues  of  the  healthy  individual  is  very  small,  in 
the  case  of  an  infected  individual  or  of  one  who  has  been  immunised 
with  tuberculin  the  amount  may  become  very  considerable  ;  this,  how- 
ever, is  not  always  so,  and  some  cases  make  good  progress  although 
the  amount  of  lysin  appears  to  be  minimal  throughout  the  course  of 
the  disease.  It  must  also  be  mentioned  that  the  tissue-cells  of  a  tuber- 
culous individual  appear  to  differ  from  those  of  a  normal  individual  in 
regard  to  the  way  in  which  they  behave  to  the  tubercle  bacillus.  This 
question  will  be  fully  dealt  with  under  the  heading  of  the  "Tuberculin 
Reaction,"  and  it  must  here  suflice  to  state  that  to  this  acquired  con- 
dition the  term  "allergic,^'  or  "  hypersensitiveness,"  has  been  applied. 
Personally  I  believe  that  the  difference  in  behaviour  of  tuberculous  and 
of  non-tuberculous  tissues  is  entirely  one  of  degree  and  not  of  kind,  and 


198  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

that  a  similar  difference  is  of  universal  occurrence,  no  matter  what  the 
variety  of  the  infective  agent  may  be. 

This  brief  account  will  suffice  to  show  the  magnitude  of  the  diffi- 
culties encountered  in  the  endeavour  to  find  an  effective  weapon  for 
combating  invasion  by  the  B.  tuberculosis. 

Furthermore,  the  great  tendency  of  the  tissues  to  surround  the 
invaders  with  a  more  or  less  impenetrable  zone  of  fibrous  tissue,  espe- 
cially well  shown  in  cases  of  chronic  lupus,  and  also  in  cases  of 
chronic  phthisis,  and  the  avascular  character  of  the  tubercles,  renders 
almost  hopeless  any  attempt  to  bring  about  a  "  sterilisam  magna  " 
comparable  to  that  which  may  be  effected  with  salvarsan  in  infections 
by  the  Spirochceta  pallida.  For  the  same  reason,  granted  that  powerful 
lytic  or  bactericidal  sera  could  be  prepared,  their  use  would  seem  fore- 
doomed to  failure  in  most  instances,  while  in  those  cases  in  which  the 
lytic  serum  could  gain  access  to  the  bacteria  the  inevitable  result  would 
be  the  rapid  flooding  of  the  tissues  with  massive  doses  of  the  endo- 
toxins thereby  liberated,  and  the  probable  death  of  the  sufferer. 

It  would  thus  appear  that  any  procedure  directed  to  the  extinction 
of  a  tuberculous  infection  must  perforce  in  its  action  be  slow  and 
gradual,  and  must  maintain  the  protective  mechanism  at  a  constant 
high  level.  The  belief  that  this  can  best  be  brought  about  by  a 
methodical  and  carefully  conducted  course  of  inoculation  with  the 
products  of  the  tubercle  bacillus  itself  is  the  justification  for  the 
advocacy  of  the  routine  employment  of  tuberculin  therapy.  This  will 
require  supplementing  by  all  the  various  measures  which  clinical 
experience  has  found  of  profit,  such  as  (i)  an  ample  supply  of  food 
which  is  easily  digestible  and  so  capable  of  being  readily  converted  to 
the  needs  of  cell  nutrition  ;  (2)  abundance  of  pure  air  whereby  the 
tissue-cells  may  be  assisted  in  their  metabolic  activities;  (3)  a  sufficiency 
of  sound  sleep  to  rest  the  actively  functioning  cells,  and  inasmuch  as 
weakly  cells  necessarily  require  more  rest  than  healthy  ones,  the  tuber- 
culous individual  requires  to  rest  his  more  than  the  normal  person  ;  (4) 
for  a  similar  reason,  hyperactivity,  either  of  the  mind  or  body,  should 
be  avoided,  especially  in  view^  of  the  influence  exerted  thereby  upon  the 
blood-supply  to  the  tuberculous  foci ;  (5)  all  toxic  influences  which 
may  damage  the  tissue-cells  must  be  rigidly  limited,  and,  if  possible^ 
removed.  Toxic  absorption  from  the  gums,  tonsils  and  nose  due  to 
conditions  of  pyorrhoea  alveolaris,  follicular  tonsillitis  and  chronic 
catarrh,  and  from  the  bowels,  due  to  intestinal  stasis,  are  especially 
prejudicial  to  the  tuberculous,  and  should  receive  the  strictest  care  and 
attention.  Similarly  toxic  absorption  from  areas  infected  by  the 
tubercle  bacillus  and  allied  invaders  must  be  limited  except  in  so  far 
as  it  is  serving  a  useful  purpose  in  the  production  of  immunity. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  1 99 


Tlic  Tuberculins  and  their  Use  in  the  Diagnosis  of  Pulmonary  Tuberculosis. 

The  preparations  of  the  tubercle  bacillus  for  therapeutic  purposes 
are  made  either  from  the  bodies  of  the  bacilli  themselves,  from  the 
iiuid  medium  in  which  thev  have  been  cultured,  or  from  a  mixture  of 
the  fluid  medium  and  of  extractives  from  the  bacilli.  Their  number 
now  is  very  great  and  only  the  more  commonly  used  and  important 
ones  will  be  mentioned. 

From  the  culture  fluid. — (i)  T.O.A.  is  simply  the  fluid  in  which  the 
bacteria  of  the  human  type  have  grown,  unaltered  in  any  way  except 
that  the  baciUary  bodies  have  been  removed  by  filtration  through  a 
Chamberland  candle. 

The  corresponding  preparation  from  the  bovine  strain  is  known  as 
P.T.O.,  not  P.T.O.A. 

(2)  \'acuum  tuberculin  is  T.O.A.  which  has  been  concentrated  by 
evaporation  at  a  low  temperature  in  a  partial  vacuum  to  one  tenth  its 
original  bulk.  Deny"s  tuberculin  corresponds  closely  to  this  prepara- 
tion. The  corresponding  bovine  preparation  is  designated  bovine 
vacuum  tuberculin. 

(3)  T.,  or  old  tuberculin,  is  prepared  from  a  four  to  five  weeks' 
old  culture  of  the  human  type  bacillus  in  glycerine  broth  in  the 
following  way :  The  cultures  are  treated  with  steam  for  half  an  hour 
to  insure  sterility  :  they  are  then  placed  in  steam-heated  vessels  fitted 
with  a  vacuum  apparatus,  and  evaporation  is  conducted  at  70"  C.  until 
the  volume  is  reduced  by  nine  tenths.  Filtration  through  porcelain 
candles  is  then  performed,  the  filtrate  allowed  to  cool,  and  0*5  per  cent. 
phenol  added.  Sedimentation  of  indifferent  substances  is  allowed  to 
proceed  in  a  cool  place  for  several  weeks  :  these  are  removed  by 
filtration,  the  clear  filtrate  now  constituting  old  tuberculin  or  T., 
which  differs  thus  from  T.O.A.  and  vacuum  tuberculin  not  only  in  the 
fact  that  concentration  has  been  produced  with  the  aid  of  heat,  but 
also  in  that  the  bacilli  have  been  partly  extracted  with  hot  steam,  the 
albumin  and  some  of  the  globulin  of  the  bacillary  bodies  thus  being 
taken  into  solution. 

The  corresponding  bovine  preparation  is  known  as  P.T. 

From  the  bodies. —  iT)  T.O.  :  The  bacilli  are  finely  triturated  and 
extracted  with  water  until  all  the  constituents  soluble  therein  are 
removed  ;  this  solution  of  the  soluble  constituents  was  designated  T.O. 
bv  Koch,  and  regarded  by  him  as  of  no  therapeutic  value.  It  is  sup- 
posed to  contain  nothing  but  toxin.  As  we  have  already  seen,  the 
extracted  substance  is  an  albumm.      (Note  that  P.T.O.  is  the  bovine 


200  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

preparation  corresponding  to  T.O.A.,  and  not  to  T.O.,  as  might  well 
be  imagined.)  The  bacillary  residue,  after  the  extraction  with  water 
is  complete,  is  utilised  for  the  preparation  of  T.R. 

(2)  T.R.  :  The  triturated  bacillary  residue  is  alternately  treated 
with  water  and  centrifugalised  ;  after  each  centrifugalisation  the  super- 
natant fine  suspension  is  pipetted  off.  These  emulsions  are  finally 
bulked  together,  and  concentrated  by  the  aid  of  heat  and  20  per  cent. 
glycerine  added  to  constitute  T.R.  The  amount  of  solid  matter 
in  each  cubic  centimetre  is  derived  from  an  initial  10  mgrm.  of 
tubercle  bacilli,  and  the  concentration  is  conducted  until  2  mgrm. 
of  solid  substance  are  present  in  the  emulsion.  T.R.  is  thus  com- 
posed of  such  portions  of  the  bacillus  as  are  insoluble  in  water,  i.  e.  of 
some  of  the  globulin,  of  the  fatty  envelope,  and  the  essential  proto- 
plasmic casein  or  para-nucleo  albumen. 

The  corresponding  bovine  preparation  is  designated  P.T.R. 

(3)  Vacuum  T.R.  is  precisely  similar  in  method  of  preparation  to 
T.R.,  except  that  the  necessary  concentration  of  the  bulked  suspensions 
is  conducted  in  a  vacuum  instead  of  by  the  aid  of  heat. 

(4)  B.E.,  or  bacillary  emulsion,  is  prepared  by  triturating  the  whole 
bacillary  bodies,  and  emulsifying  each  0*5  grm.  of  the  powder  with  a 
mixture  of  5o<:.c.  glycerine  and  50  c.c.  distilled  water.  Each  cubic  centi- 
metre therefore  contains  5  mgrm.  of  bacillary  substance,  from  which 
nothing  has  been  removed  by  the  aid  of  solvents. 

The  corresponding  bovine  preparation  is  designated  P.B.E. 

(5)  S.B.E. :  Sensitised  bacillary  emulsion,  or  tuberculosis  sero- 
vaccine,  is  prepared  as  follows  :  Bacilli  of  the  human  type  are  collected 
on  a  filter,  and  thoroughly  washed  with  normal  salt  solution.  They 
are  then  placed  in  a  suitable  quantity  of  a  specific  tuberculosis  immu- 
nising serum  derived  from  an  animal  which  has  been  immunised 
with  living  human-type  bacilli  and  triturated  by  agitation  with 
beads  ;  the  disintegration  of  the  bacilli  is  assisted  by  heating  the 
mixture  of  bacilli  and  serum  together  at  37°  C.  for  a  long  time.  When 
the  trituration  of  the  bacilli  is  complete  the  mixture  is  centrifugalised, 
the  sediment  repeatedly  washed  with  normal  salt  solution,  and  finally 
emulsified  with  50  per  cent,  glycerine  solution,  i  c.c.  of  the  emulsion 
containing  5  mgrm.  of  solid  matter.  The  idea  of  this  preparation  was 
that  a  fixation  of  the  specific  immune  bodies,  present  in  the  serum  of 
the  immunised  animal,  should  be  effected  with  the  tubercle  bacilli. 
The  idea  does  not  seem  to  be  realised  in  actual  practice,  despite  the 
favourable  reports  of  Citron. 

From  the  culture  fluid  and  extractives  from  the  bacilli. — T.  Bk.  or 
Beraneck's  tuberculin  differs  from  the  preceding  preparations  in  that 
it  is  composed  not  only  of  the  toxins  diffused  into  the  culture  medium, 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  20I 

but  also  of  substances  extracted  from  the  bacillar}'  bodies  by  the  aid  of 
orthophosphoric  acid.  With  the  aim  of  keeping  the  product  as  free  as 
possible  from  toxic  but  non-immunising  substances,  the  broth  in  which 
the  bacilli  are  grown  contains  neither  peptone  nor  albumose.  When 
free  growth  has  occurred  the  bacilli  are  removed  b}-  filtration,  and  an 
extract  of  the  bacillary  protein  made  with  the  aid  of  a  i  per  cent, 
solution  of  orthosphoric  acid  ;  equal  portions  of  this  extract  and  of  the 
culture  medium  which  has  previously  been  evaporated  down  at  a  low 
temperature  in  vacuo  to  a  tenth  of  its  bulk  are  mixed  together  to  form 
the  finished  product.  Beraneck  claims  that  this  preparation  is  not 
onh'  as  potent  as  any  other  preparation  in  stimulating  the  formation  of 
immune  bodies,  but  that  it  is  also  much  less  toxic,  so  that  more  powerful 
immunising  effects  can  be  produced  without  giving  rise  to  undesirable 
reactions.  Sahli  supports  this  contention  ;  but  from  the  description  of 
some  of  the  reactions  obtained  in  his  cases,  it  would  seem  that  its 
toxicity  for  tuberculous  guinea-pigs  is  no  measure  of  its  toxicity  for 
tuberculous  human  beings.  Nevertheless,  there  is  something  to  be 
said  theoretically  in  its  favour,  and  further  clinical  experience  may 
confirm  the  claims  made  on  its  behalf. 

Landmann's  tuberculol  is  somewhat  similar  and  is  prepared  as 
follows  :  Broth  cultures  of  highly  virulent  bacilli  after  being  freed  from 
fat  and  finely  powdered  are  extracted  with  normal  saline  or  dilute 
glycerine  for  some  time  at  40°  C. ;  the  residue  is  repeatedly  extracted 
with  fresh  fluid  at  a  temperature  which  is  gradually  raised  to  100"  C. 
The  extracts  are  mixed  and  the  total  product  concentrated  in  vacuo  at 
37°  C.  This  is  then  added  to  the  culture  fluid  which  has  been  concen- 
trated in  vacuo  as  far  as  possible  and  the  whole  filtered  through  porce- 
lain candles ;  carbolic  acid  is  then  added  to  make  0*5  per  cent.,  and  the 
preparation  is  diluted  until  i  cc.  just  suffices  to  kill  a  guinea-pig 
weighing  250  grm.  This  preparation  has  the  advantage  of  accurate 
standardisation  of  its  toxin  content ;  the  disadvantage,  according  to 
Beraneck,  of  not  only  containing  much  non-specific  toxin  but  also  of 
containing  an  undue  amount  of  specific  toxin  relative  to  its  power  of 
exciting  immunising  response. 

The  doubt  existing  as  to  whether  the  strains  of  tubercle  bacilli 
infecting  man  are  identical  in  every  instance,  or  whether  they  merely 
closely  resemble  each  other  as  do  the  various  streptococci,  has  led  to 
manufacturers  employing  cultures  of  strains  derived,  not  from  one,  but 
from  several  sources  ;  to  the  preparation  derived  therefrom  the  term 
"  polygenous  "  has  been  prefixed,  viz.  polygenous  bacillary  emulsion. 
This  I  have  long  advocated  and  am  convinced  is  a  step  in  the  right 
direction. 

Numerous    attempts    have  also  been   made  to   bring  about   active 


202  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

immunisation  on  lines  parallel  to  those  introduced  by  Jenner  for  small- 
pox and  by  Pasteur  for  rabies  and  anthrax.  To  this  end  bacilli  either 
of  attenuated  virulence  or  devoid  of  pathogenic  power  for  man  have 
been  employed  by  Klimmer  and  by  Friedmann.  Klimmer  utilises 
human  bacilli  which  have  been  completely  deprived  of  their  infecting 
power  by  long  heating  to  52°  C.  or  by  passage  through  animals  ;  these, 
he  states,  do  not  regain  their  virulence  when  introduced  into  the  human 
tissues.  Friedmann  has  just  introduced  an  avirulent  preparation 
derived  from  a  tuberculous  giant  tortoise  and  claims  the  most  striking 
successes.  His  claims,  like  those  of  Klimmer,  require  further  confirma- 
tion ;  on  mere  a  priori  reasoning  they  seem  likely  to  require  consider- 
able qualification. 

The  Tubercidins  in  the  Diagnosis  of  Pulmonary  Tiiberculosis ;  "  Allergie" 

or  "  Reactivity." 

Whereas  doses  of  i  c.c.  or  even  5  c.c.  of  old  tuberculin  have 
been  introduced  subcutaneousfy  into  the  tissues  of  an  individual 
entirely  free  from  active  tuberculosis  without  producing  an}'  appreci- 
able disturbance,  constitutional  or  otherwise,  quite  otherwise  is  it  with 
infected  individuals,  in  whom  relatively  minute  doses  act  as  a  powerful 
poison  and  produce  a  train  of  characteristic  symptoms.  Infection  has 
brought  about  a  condition  of  their  tissues  not  present  in  those  of  the 
healthy,  a  condition  to  which  the  terms  "allergic,"  "reactivity"  or 
"  sensitiveness  "  have  been  applied.  In  the  healthy  the  albumin  of 
the  tuberculin  is  dealt  with  like  any  other  foreign  albumin,  and  a  con- 
dition of  anaphylaxis  can  be  induced  if  the  initial  dose  of  tubercular 
endoplasm  be  sufficiently  large.  In  the  infected  it  is  dealt  with 
apparently  in  quite  another  way :  the  presence  of  living  tubercle  bacilli 
in  the  tissues  has  brought  about  an  obscure  change  in  the  cells  whereby 
they  are  enabled  to  break  down,  more  or  less  slowly,  the  albumin  of 
tuberculin  into  a  toxic  and  a  non-toxic  portion.  Wolff-Eisner  has 
suggested  the  term  "  tuberculo-lysin "  for  the  unknown  substance 
whereby  this  is  brought  about.  The  theory  is  not  an  entirely  satis- 
factory one,  but  it  is  simple  and  explains  most  observed  facts.  All 
the  methods  wherein  tuberculin  is  utilised  for  the  diagnosis  of  tuber- 
culous infection  depend  upon  the  presence  in  the  tissues  of  this  hypo- 
thecated tuberculo-lysin,  which,  as  has  been  stated,  is  only  formed 
when  living  tubercle  bacilli  are  resident  in  the  tissues. 

The  cntaneons  test  of  von  Pirquet  is  performed  as  follows  :  The  skin 
on  the  inner  side  of  the  forearm  is  rubbed  with  ether,  one  drop  of  a  25 
per  cent,  dilution  of  old  tuberculin  is  placed  thereon,  and  4  in.  below 
it  a  drop  of  undiluted  tuberculin.  By  means  of  a  platinum  inoculation 
needle  a  circular  scarification,  just  penetrating  the  epidermal  layer  as 


THE    BACTERIAL    DISEASES    OF    RESPIRATIOX.  20 3 

in  ordinary  vaccination,  is  made  midwa}-  between  the  two  drops.  The 
operation  is  then  repeated  on  the  skin  underlying  the  25  per  cent,  dilu- 
tion, and  lastly,  at  the  site  of  the  undiluted  drop.  After  the  inoculation 
the  tubercuHn  is  allowed  to  soak  into  the  tissue  spaces  for  some  minutes 
or  a  minute  piece  of  cotton-wool  is  applied  to  each  area,  no  other 
dressing  being  required.  Inspection  is  to  be  made  at  the  end  of 
twenty-four  and  forty-eight  hours,  and  if  no  reaction  be  then  apparent 
again  at  seventy-two  and  ninety-six  hours.  In  interpreting  the  results 
it  is  necessary  to  distinguish  between — 

(i)  The  traumatic  reaction  due  to  the  scarification. 

(2)  The  negative  reaction. 

(3)  The  positive  reaction. 

The  traumatic  reaction  begins  within  a  few  minutes  at  each  locality  ; 
at  first  it  consists  of  a  small  raised  area  surrounded  by  a  red  areola, 
which  disappears  within  a  few  hours  ;  there  remains  only  a  slightly 
raised  redness,  with  a  papule,  about  as  large  as  a  pin's  head,  in  the 
centre.  After  twenty-four  hours  only  a  little  redness  in  the  immediate 
area  of  the  scarification  is  to  be  seen :  this  soon  disappears,  a  small 
brown  scab  remaining  for  the  next  few  days. 

In  the  case  of  negative  reactions  an  appearance  similar  to  that 
at  the  control  area  is  presented  ;  the  distinction  from  minimal  specific 
reactions  is  by  no  means  easy,  and  von  Pirquet  advises  that  reactions 
under  5  mm.  in  diameter  should  be  regarded  as  doubtful,  and  definite 
judgment  suspended  until  repetition  has  been  m.ade,  as  thereby  the 
signs  of  a  positive  reaction  are  accentuated. 

In  the  positive  reaction  there  is  a  latent  period  varying  from  three 
hours  to  several  days,  during  which  nothing  more  than  the  correspond- 
ing traumatic  reaction  is  to  be  seen.  In  most  cases  it  is  well  developed 
after  twenty-four  hours  and  most  distinct  at  the  end  of  forty-eight 
hours;  if  not  seen  till  later  it  is  called  "torpid."  It  begins  as 
hyperaemia  and  exudation,  and  appears  as  a  slight  red  swelhng, 
commencing  in  the  punctures,  and  rapidly  developing  in  area  and 
height;  the  edge  of  the  papule  is  sometimes  rounded,  sometimes 
indented ;  occasionally  it  is  surrounded  by  a  flat,  slightly  bluish 
areola,  from  the  margin  of  which  reddened  lymphatics  may  be  traced. 
As  a  rule  the  papule  measures  about  10  mm.  in  diameter,  occasionally 
20  mm.,  and  rarely  in  cases  of  very  severe  reaction  30  mm.  The 
maximum  reaction  is  usually  attained  in  forty-eight  hours  :  the  exuda- 
tion then  begins  to  decrease,  the  redness  fades,  passes  into  violet  and 
gradually  into  a  pigmentation  which  may  persist  for  weeks  ;  the 
epidermis  usually  peels  slightly.  Rarely  the  papule  is  colourless  and 
can  only  be  felt. 

A  positive  reaction  is  not  accompanied  by  any  rise  of  temperature  or 


204  THE    BACTERIAL   DISEASES    OF    RESPIRATION. 

other  constitutional  disturbance,  and  if  the  test  is  properly  conducted 
never  gives  rise  to  any  complications  or  sequelae.  It  gives  indication  of 
a  specific  tuberculous  infection,  but  gives  no  information  as  to  the 
nature  or  site  of  the  lesion,  of  its  activity  or  quiescence ;  it  only 
indicates  that  infection  has  occurred  at  some  time  and  place. 

A  negative  reaction  is  strong  evidence  of  the  absence  of  tubercu- 
losis, but  is  sometimes  seen  in  the  last  days  of  a  fatal  tuberculosis,  in 
the  final  stage  of  miliary  tuberculosis  or  tubercular  meningitis, 
occasionally  in  tuberculosis  complicated  by  some  other  disease,  and  in 
advanced  cachectic  conditions. 

Inasmuch  as  over  go  per  cent,  of  all  adults  have  been  infected 
with  tuberculosis  at  some  period  or  other  of  their  lives  the  diagnostic 
significance  of  the  test  is  very  greatly  reduced,  and  its  value  as  an 
indication  of  active  tuberculosis  can  only  be  accepted  in  children  up  to 
the  age  of  three  or  four  years,  in  whom  healed  tuberculosis  is  a  rare 
phenomenon. 

The  attempt  has  been  made  by  Sahli  and  others  to  so  modify  the 
test  as  to  enable  it  to  be  employed  as  a  measurement  of  the  sensitive- 
ness or  reactivity  of  the  tissues,  and  so  as  an  indication  of  the 
appropriate  dosage  of  tuberculin  for  therapeutic  purposes.  To  this  end 
the  test  is  made  in  turn  with  dilutions  of  i  in  lo,  i  in  lOO,  i  in 
1000,  and  if  necessary  i  in  10,000,  that  dose  being  considered  to  be 
the  one  suitable  for  subcutaneous  use  which  corresponds  to  half  that 
minimal  quantity  which  gives  a  positive  reaction. 

Morro's  percntaneoiLS  test  is  conducted  as  follows :  The  skin  on  the 
inside  of  the  forearm  or  just  below  the  tip  of  the  ensiform  cartilage 
is  rubbed  well  with  ether.  A  piece  of  ointment  as  large  as  a  pea, 
prepared  by  mixing  thoroughly  together  at  a  temperature  of  20°  C. 
equal  parts  of  lanoline  and  old  tuberculin,  is  then  rubbed  in  with 
moderate  pressure  by  the  finger-tip  for  half  to  one  minute  over  an  area 
of  about  5  cm.  diameter.  As  with  the  cutaneous  test  so  different  grades 
of  reaction  are  presented  by  the  percutaneous  test,  varying  from  the 
appearance  after  twenty-four  to  forty-eight  hours  of  isolated  reddened 
spots  to  papules  indistinguishable  in  size  and  appearance  from  those 
produced  by  the  von  Pirquet  test.  As  a  rule,  a  number,  twenty  to 
thirty,  of  discrete  miliary  nodules  with  reddened  areola  are  produced, 
accompanied  by  itching  and  lasting  for  several  days,  after  which 
there  is  some  pigmentation  and  peeling  of  the  skin.  Of  the  specificity 
of  the  test  there  is  no  doubt,  but  its  reliability  is  distinctly  inferior  to 
that  of  the  cutaneous  test. 

De  Carle  Woodcock  blister  reaction  is  a  modification  of  Von 
Pirquet's  test.  Two  small  blisters  are  applied  to  the  skin  of  the  back, 
of  the  chest,  or  other  locality.     When  the  skin  has  risen  it  is  removed 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  20 5 

with  scissors  and  a  water  dressing  applied  for  twenty-four  hours  to 
remove  the  hypercemia.  To  one  of  the  denuded  areas  a  drop  of 
undiluted  T.R.  is  applied  and  allowed  to  dry — this  takes  about  half  an 
hour ;  a  dressing  of  dry  lint  is  then  applied  to  both  areas,  and  these 
are  compared  after  twenty-four  hours.  If  tuberculosis  be  present,  the 
surface  treated  with  tuberculin  is  then  rosy  red  with  a  blush  on  its 
circumference,  and  there  is  some  exudation  ;  the  untreated  surface  is 
comparatively  pale.  The  test  is  more  complicated,  occupies  more  time, 
and  appears  to  possess  little  advantage  over  the  von  Pirquet  test. 

The  intra-dermal  test  of  Mantoux. — A  solution  of  i  in  5000  of  old 
tuberculin,  to  which  stovaine  to  make  o'5  per  cent,  is  added  in  order 
to  diminish  the  resultant  pain,  is  employed  for  this  test.  The  skin  is 
washed  wath  alcohol  or  ether,  and  by  means  of  a  line  short  needle 
I  drop,  or  o"05  c.c,  of  the  solution  is  introduced,  so  that  it  lies  just 
beneath  the  epidermis  and  over  the  hypodermis.  In  order  to  secure 
this  result  the  syringe  must  be  perfectly  air-tight,  the  exit  of  the 
needle  point  must  be  turned  towards  the  surface  of  the  skin  and 
the  fluid  gently  expressed ;  it  should  then  be  apparent  as  a  little  drop 
of  cedema  about  4  mm.  in  diameter. 

A  positive  reaction  is  indicated  by  the  appearance  after  four  to 
eight  hours  of  an  infiltration,  white  or  rosy  red  in  colour.  This  rapidly 
extends,  and  at  the  end  of  twenty-four  to  forty-eight  hours,  when  the 
reaction  is  at  its  height,  the  infiltrated  area  is  rosy  or  bright  red,  rarelv 
pale,  and  is  |  to  i.^  in.  in  diameter.  It  is  surrounded  by  an  erythema- 
tous area  of  considerable  extent,  so  that  the  whole  reactive  zone  may 
be  covered  by  the  palm  of  the  hand.  After  two  or  three  days  the 
reaction  begins  to  disappear. 

This  test  is  even  more  delicate  than  that  of  von  Pirquet  in  revealing 
the  presence  of  latent  tuberculosis,  and  is  at  least  as  reliable  for  the 
detection  of  active  foci.  In  accompanying  advanced  cachectic  states 
and  measles,  and  in  meningitis  and  advanced  stages  of  the  disease,  the 
reaction  may,  however,  fail. 

The  chief  interest  of  the  test  lies  in  the  endeavours  which  have  been 
made  to  utilise  it  as  a  measure  of  the  reactive  power  of  the  tissues, 
and  so  to  aid  in  prognosis  and  the  determination  of  dosage.  To  this 
end,  the  skin  over  an  area,  say,  of  one  or  two  centimetres  is  picked  up 
by  means  of  calipers  and  its  thickness  measured  and  compared  with  that 
of  a  similar  area  of  skin  at  the  corresponding  site  of  the  body  where 
inoculation  has  not  been  performed.  By  repeating  the  test  with 
dilutions  of  tuberculin  weaker  or  stronger  than  that  given  above,  a 
dilution  may  then  be  found  which  will  induce  an  increase  in  thickness 
of  the  skin  of  any  desired  dimension.  No  definite  results  have  as  yet 
been  obtained,  but  the  procedure  is  well  worthy  of  further  investigation. 


,2o6  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

The  Ophthahno-Test  of  Cahnette  and  Wolff-Eisner. 

For  the  performance  of  this  test  Calmette  recommends  a  tuberculin 
prepared  by  precipitating  bovine  tuberculin  with  95  per  cent,  alcohol, 
and  freed  by  a  complicated  process  from  glycerine,  resin,  and  wax,  but 
still  containing  the  potent  bacterial  bodies ;  the  precipitate  is  then 
dissolved  in  distilled  water  to  form  solutions  of  0*5,  i,  2,  and  4  per 
cent,  strength.  Bandelier  and  Roepke  advise  that  the  old  tuberculin 
of  Koch  should  be  diluted  with  o"85  per  cent,  sterile  salt  solution,  or 
with  o"5  per  cent,  solution  of  carbolic  acid  in  water,  and  state  that  this 
in  1-4  per  cent,  dilutions  of  the  tuberculin  is  unirritating  to  the 
healthy  eye. 

For  a  first  test  Calmette  advises  the  0*5  dilution,  and  this  is  usually 
employed  in  this  country;  Bandelier  and  Roepke  advise  the  I'o  per 
cent,  dilution. 

The  test  is  performed  as  follows  :  The  patient  sits  on  a  chair,  and 
throws  the  head  slightly  backwards.  The  physician  draws  down  the 
lower  lid,  and  lets  one  drop  of  the  selected  dilution  fall  gently  from  a 
drop-pipette  into  the  lower  conjunctival  sac.  The  lid  is  kept  retracted 
for  half  a  minute,  so  that  the  conjunctiva  is  well  bathed  with  the  solu- 
tion ;  the  patient  then  looks  upwards  with  the  lids  open  for  a  similar 
period.  The  eye  should  not  be  bandaged,  and  the  patient  should  be 
warned  against  subsequent  rubbing  of  the  eye. 

The  reaction  may  begin  in  four  or  five  hours,  but  usually  does  so 
within  twelve  hours,  and  is  at  its  height  after  an  interval  of  twenty- 
four  to  thirty-six  hours  ;  occasionally  response  is  delayed  for  two  or 
three  days.     Three  grades  of  reaction  are  distinguished  : 

(i)  Slight — reddening  of  the  caruncle  and  palpebral  conjunctiva 
with  some  lachrymation. 

(2)  Moderate — intenser  reddening  with  increased  secretion,  and 
reddening  of  the  ocular  conjuntiva  ;  threads  of  fibrinous  secretion  may 
be  seen  in  the  conjunctival  cid-de-sac. 

(3)  Severe — intense  reddening  of  the  whole  conjunctiva,  with 
chemosis,  much  fibrinous  and  purulent  secretion,  photophobia,  and 
perhaps  small  ecchymoses. 

In  no  case  should  there  be  rise  of  temperature  or  pain.  The  eye 
should  resume  its  normal  appearance  in  two  or  three  days  ;  occasion- 
ally this  occupies  five  or  six  days,  rarely  ten  to  fifteen  days. 

In  the  event  of  a  positive  reaction  not  being  obtained,  some 
authorities  advise  the  repetition  of  the  test  two  days  later  upon  the 
same  eye  with  a  tuberculin  of  double  strength,  and  if  this  fail  a  further 
repetition  two  days  later  with  a  tuberculin  again  doubled  in  concentra- 
tion.    This  procedure  is,  however,  free  from   danger  only  when  due 


THE    BACTERIAL    DISEASES    OF    RESPIRATIOX.  207 

regard  is  paid  to  certain  contra-indications  which  are  equally  applic- 
able to  the  first  instillation  ;  thus,  according  to  Calmette,  absolute 
contra-indication  is  given  by  any  ocular  disease,  no  matter  the  kind  or 
stage,  even  if  the  processes  have  run  their  course.  Unsoundness  of 
one  eye  forbids  the  test  being  applied  to  the  other.  In  children  severe 
reactions  are  especially  liable  to  occur,  and  in  them  the  application  of 
the  test  is  best  avoided. 

So  many  serious  results  have  now  been  recorded  by  careful  and  com- 
petent observers  that  the  test  has  fallen  into  some  disrepute,  and  is 
perhaps  best  left  in  the  hands  of  specialists.  Personally,  I  have  never 
experienced  any  difficulty  nor  seen  any  ill-results  come  from  it. 

Wolff  and  Bandelier  and  Roepke  report  one  peculiar  difficulty 
which  is  liable  to  arise,  namely,  a  recrudescence  of  the  reaction  after 
therapeutic  inoculations  with  minimal  doses  of  tuberculin — an  effect 
which  may  be  so  constant  and  so  persistent  as  to  necessitate  a  suspen- 
sion of  the  tuberculin  treatment. 

The  diagnostic  value  of  the  test. — Repetition  of  the  instillation  has  been 
opposed  by  various  authorities  on  the  ground  that  a  previous  instillation 
is  able  to  set  up  a  condition  of  hypersusceptibility  in  the  tissues  of  a 
truly  healthy  individual.  This  is  almost  certainly  wrong,  and  the 
frequency  with  which  positive  results  have  been  reported  in  sufferers 
from  typhoid  and  scarlet  fever,  syphilis,  diabetes,  etc.,  who  were  stated 
to  be  free  from  tubercle,  is  probably  due  to  the  fact  that  these 
individuals  were  only  clinically  free  from  tubercle,  and  in  reality 
possessed  latent  or  healed  foci.  A  comparison  of  the  results  it  yields 
with  those  given  by  the  cutaneous  test  strongly  confirms  its  true 
specificity. 

Very  cachectic  cases  and  those  suffering  from  very  advanced  phthisis 
may  fail  to  give  a  positive  reaction  just  as  they  will  fail  towards  the 
cutaneous  and  subcutaneous  tests.  At  the  same  time  there  is  no 
doubt  that  it  does  not  give  a  correct  indication  in  a  certain  number 
of  cases  where  it  might  be  anticipated  with  considerable  confidence, 
and  it  is  unfortunately  the  case  that  one  or  even  two  instillations  may 
especially  fail  to  give  correct  guidance  just  in  those  cases  where  it 
is  most  needed,  i.e.  in  the  early  stages  of  pulmonary  tuberculosis. 
Furthermore,  the  fact  that  a  case  of  perfectly  quiescent  phthisis  may 
react  strongly  to  a  first  instillation,  while  one  with  active  mischief  may 
require  at  least  three,  tends  further  to  limit  the  practical  utility  of 
the  test. 

The   Subcutaneous  Test  and  the   Tuberculin  Reaction. 
For  the  subcutaneous  test  Koch"s  old  tuberculin  is  employed,  and 
the  procedure  is  as  follows  :     The  mouth   temperature  is  taken  every 


208  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

three  hours,  and  if  it  prove  to  go  over  37-2°  C,  or  99°  F.,  the  patient 
remains  in  bed  until  it  has  not  risen  above  this  level  for  at  least  two 
days.  No  attempt  at  reduction  by  means  of  drugs  is  permissible. 
The  test  should  never  be  applied  to  females  during  or  near  the 
menstrual  period. 

The  skin  at  the  inferior  angle  of  the  scapula  is  sterilised  and  the 
inoculation  performed  aseptically.  The  appropriate  initial  dosage 
varies  according  to  different  authorities,  but  the  following  is  perhaps 
the  best :  In  weakly  subjects  and  in  suspected  early  cases  in  whom 
reactions  are  often  marked,  begin  with  -oooi  c.c. ;  with  strong  people 
begin  with  •ooo2-"ooo5  c.c. ;  with  children  with  "oooos-'oooi  c.c.  If 
there  is  no  reaction  within  twenty-four  hours,  such  as  will  be  described, 
the  procedure  may  be  tabulated  as  follows  : 

^^^Griklv  subiGcts 
After  interval  of  Children.  and  early  cases.  Strong  subjects. 

Two  days     .       "0002  c.c.  .  '0005  c.c.  .  'ooi  c.c. 

•0005  ,,  .  -001    ,,  .  -005     „ 

•002  ,,  .  -005    ,,  .  -01    „ 

•002   ,,  .  -005    ,,  .  -01     „ 

A  definite  reaction  consists  in  a  rise  of  temperature  of  o'5°  C.  or 
1°  F;,  a  doubtful  reaction  in  a  rise  of  o'3°C.  or  o'5°  F.  In  the  former 
case  the  experiment  is  concluded  at  that  stage  which  gave  the  reaction. 
In  the  latter  case  the  dosage  is  not  increased,  but  is  repeated  on  the  day 
following  that  on  which  the  temperature  returns  to  normal ;  a  definite 
reaction  is  then  shown  by  a  rise  of  temperature  greater  than  before,  a 
negative  reaction  by  a  smaller  rise. 

If  a  negative  reaction  is  obtained  with  the  fourth  inoculation,  that 
dosage  should  be  repeated  once  in  all  strongly  suspected  cases  to  exclude 
definitely  the  diagnosis  of  tuberculosis. 

Absolute  contra-indications  to  the  use  of  the  subcutaneous  test 
are — 

(i)  A  rise  of  temperature  to  over  37"2°  C.  which  will  not  yield  to 
rest. 

(2)  The  presence  of  tubercle  bacilli  in  the  sputum. 

(3)  The  fact  that  a  definite  diagnosis  is  already  possible. 
Other  conditions  which  may  contra-indicate  the  test  are — 

(i)  Haemoptysis  ;  this,  however,  only  necessitates  waiting  till  all 
blood  has  disappeared  for  a  week  from  the  sputum,  whereby  full 
opportunity  is  afforded  for  the  healing  of  the  vessel,  a  possible  reduc- 
tion of  the  initial  dosage  and  cautious  increase  of  subsequent  ones. 

(2)  Renal  disease  as  evidenced  by  albumen,  blood  and  casts  in  the 
urine.  Only  severe  cases  are  excluded  from  the  test,  in  others  careful 
dosage  is  advisable. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  209 

(3)  Heart  disease,  but  only  if  there  be  severe  valvular  disease  or 
definite  m\'ocarditis. 

(4)  Epilepsv  :  As  it  has  been  noticed  that  epileptiform  seizures  which 
have  been  in  abeyance  for  years  may  be  again  initiated,  marked  care  is 
necessarv  if  the  clinical  condition  indicates  the  advisability  of  perform- 
ing the  test. 

(5)  Diabetes  certainly  necessitates  care,  and  if  the  disease  be 
advanced  the  question  may  well  be  raised,  is  it  worth  while  ? 

(6)  Hysteria:  Here  the  result  is  apt  to  be  upset  by  psychical  rises  of 
temperature  ;  the  cutaneous  reaction  must  be  substituted  in  this  case. 

(7)  The  suspected  presence  of  miliary  tuberculosis  or  advanced 
tuberculous  ulceration  of  the  intestines,  especially  if  pain  and  tender- 
ness be  present. 

(8)  Age  :  In  young  children  under  the  age  of  three  the  cutaneous 
reaction  is  quite  reliable  and  is  to  be  preferred  ;  in  older  children  the 
subcutaneous  test  is  quite  safe  and  should  be  employed. 

Although  the  rise  of  temperature  is  the  main  point  upon  which 
most  diagnosticians  concentrate  their  attention,  it  is  only  one  of  the 
resultant  phenomena  which  may  be  encountered.  The  complete  tuber- 
culin reaction  consists  in  (i)  local,  (2)  general,  (3)  focal  disturbances. 

(i)  The  local  reaction  may  be  of  any  grade,  from  complete  absence 
to  the  production  of  a  painful  red  swelling  with  oedema  of  the  sub- 
cutaneous tissues  for  an  area  of  1-2  in.  in  diameter  around  the 
puncture,  and  of  pain  and  redness  along  the  needle  track  due  to  the 
escape  of  a  small  quantity  of  the  tuberculin  when  introducing  or  with- 
drawing the  needle. 

The  local  reaction  usually  subsides  in  two  or  three  days. 

(2)  The  general  reaction  is  due  to  toxic  effects  upon  the  central 
nervous  system.  Characteristicall}',  as  w'e  have  seen,  the  most  impor- 
tant feature  is  a  rise  of  temperature  of  at  least  0*5^  C.  or  1°  F.  A.  rise 
to  38^  C.  is  designated  "  slight,"  one  to  39°  C.  '''  moderate,"  and  one 
over  39°  C.  "  severe."  Most  typicall}^  it  consists  in  a  rise  of  tempera- 
ture which  begins  within  si.x  to  eight  hours,  reaches  a  maximum  in 
twelve  to  sixteen  hours,  and  subsides  to  normal  in  twenty-four  to  fort}'- 
eight  hours ;  in  time  of  onset,  height  and  duration  of  rise  great 
divergences  from  this  normal  course  may  be  encountered,  so  that  it  is 
hardly  possible  to  speak  of  a  typical  curve.  Sometimes  the  rise  of 
temperature  begins  within  four  hours,  sometimes  it  is  delayed  for  thirty 
hours,  sometimes  the  fall  of  temperature  is  by  crisis,  more  often  perhaps 
it  is  bv  kvsis ;    secondary  oscillations  may  be  seen. 

In  mild  forms  the  rise  of  temperature  and  a  slight  acceleration  of 
pulse  and  respiration-rate  and  a  slight  malaise  constitute  the  whole  of  the 
general  reaction  ;  more  often  there  is  some  pain   or  ache  at  the  site  of 

14 


2IO  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

infection,  some  headache  of  varying  degree,  and  more  pronounced 
malaise  and  acceleration  of  pulse  and  respiration  ;  occasionally  there  is 
very  marked  malaise,  nausea  and  vomiting,  photophobia,  rigors,  pains  in 
the  limbs,  thirst  and  sleeplessness  ;  loss  of  weight  even  up  to  one  pound 
may  also  result.  Such  severe  forms  of  the  reaction  as  this  are  especially 
liable  to  occur  with  very  slight  and  early  degrees  of  infection. 
Personally  I  have  only  met  with  them  in  such  cases  and  with  the 
initial  dosage  of  only  "oooi  c.c.  These  unpleasant  disturbances  as  a 
rule  subside  with  great  rapidity  and  no  ill-effects  whatever  remain 
after  the  lapse  of  twenty-four  hours ;  should  they  persist  there  is  no 
objection  whatever  to  the  administration  of  5  to  10  gr.  of  phenacetin  or 
antipyrin,  8  gr.  of  pyramidon,  or  10  gr.  of  bromural. 

When  the  reaction  finally  passes  off  it  generally  leaves  behind  it  a 
decidedly  increased  feeling  of  general  well-being  and  comfort  ;  in  any 
case  no  harm  ever  results  in  these  days  of  low  initial  dosage  and 
gradual  increase. 

(3)  The  focal  reaction  :  Whether  a  focal  reaction,  i.  e.  one  occurring 
at  the  site  of  the  lesion,  often  occurs  in  the  absence  of  a  preceding 
local  and  general  reaction  is  a  disputed  point.  That  it  does  sometimes 
occur  cannot  be  questioned;  some  observers,  like  Hamman  and  Wolman, 
say  they  hav.e  never  detected  an  increase  in  the  physical  signs  in  the 
lungs  without  some  evidence  of  a  general  reaction.  Carl  Spengler  has 
observed  it  preceding  the  general  reaction,  Turban  has  noticed  its 
occurrence  in  the  absence  of  the  general  reaction,  and  I  myself  have 
never  failed  to  detect  a  distinct  alteration  in  physical  signs,  preceding, 
accompanying  or  succeeding  any  general  reaction,  even  of  the  smallest 
degree.  Of  all  the  signs  of  response  to  inoculation  with  tuberculin  it 
is,  pace  many  observers,  the  most  sure,  the  most  definite  and  the  most 
easily  obtainable  with  minimal  doses  of  tuberculin,  the  essentials  for 
its  observation  being  careful  charting  of  the  physical  signs  before 
inoculation  and  at  intervals  of  four  hours  thereafter,  beginning  eight 
hours  after  the  inoculation  and  being  continued  if  necessary  till  the 
lapse  of  another  forty  hours.  The  increase  of  physical  signs  and 
symptoms  is  due  to  exudation  set  up  by  the  induced  hyperaemia,  and  is 
often  accompanied  by  slight  pain  or  ache  of  the  affected  parts  and  by 
increased  expectoration. 

Personally  I  believe  that  the  production  of  a  focal  reaction  is  an 
absolute  essential  for  the  production  of  a  general  one.  Were  the  focal 
reaction  not  an  inevitable  result  of  the  administration  of  diagnostic 
doses  of  tuberculin  how  utterly  futile  would  be  the  subsequent  treat- 
ment of  the  patient  with  the  much  smaller  therapeutic  doses,  for  on 
the  hypersemic  and  other  changes  induced  at  the  foci  of  disease  does 
the  curative  action  of  the  tuberculin  mainly  depend. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  2  I  I 

This  leads  us  to  the  consideration  of  the  theories  advanced  in 
explanation  of  the  tuberculin  reaction.  All  of  these  it  would  be  little 
profit  to  discuss,  but  two  or  three  require  mention. 

Let  us  first  see  what  are  the  main  facts  that  need  explanation. 
The}^  are  these  :  that  doses  of  even  yu  ^•^-  ^^  old  tuberculin  can  be 
administered  to  healthy  men  and  i  c.c.  to  healthy  guinea-pigs  without 
producing  any  general  disturbance  whatever,  whereas  the  administra- 
tion of  Y^wo  '^•'"-  '^^'ill)  ini  the  case  of  many  tuberculous  human  beings, 
cause  a  marked  general  reaction  and  often  kill  an  infected  guinea-pig. 
Healthy  individuals  are  thus  very  tolerant  to  the  toxin  contained  in 
tuberculin,  while  infected  ones  are  very  intolerant. 

One  suggestion  put  forward  to  explain  these  points  was  that  the 
difference  was  due  to  the  fact  that  the  injected  individual  already  con- 
tained a  considerable  amount  of  tuberculo-toxin,  and  that  a  reaction 
was  due  to  the  summation  with  this  of  the  injected  toxin.  This  mere 
summation  theory  is  quite  inadequate  to  explain  all  the  facts. 

Wassermann  and  Bruch  have  advanced  another  theory  based  on 
the  observation  that  in  the  serum  of  patients  treated  with  tuberculin, 
and  at  the  infected  foci  of  untreated  patients,  there  is  a  substance 
which,  with  tuberculin,  causes  absorption  of  complement,  and  to  this 
body  they  have  given  the  somewhat  unfortunate  name  of  "  anti-tuber- 
culin "  as  if  it  were  an  antitoxic  substance  neutralising  tuberculin, 
'instead  of  being  a  body  which  activates  tuberculin. 

They  therefore  suppose  that  reactions  occur  when  tuberculin  meets 
with  anti-tuberculin  in  the  foci  and  fixation  of  complement  results. 

Objections  to  this  theory  are  many ;  thus  it  is  difficult  to  see  how 
both  tuberculin  and  anti-tuberculin  can  exist  together  in  tubercular  foci 
'without  combining  with  each  other ;  secondly,  it  is  hard  to  understand 
how  a  combination  of  tuberculin  and  anti-tuberculin  in  which  chemical 
affinities  are  satisfied  can  cause  inflammatory  reactions ;  thirdly,  it  is 
incomprehensible  that  the  combination  can  have  a  harmful  action  on 
the  foci  and  at  the  same  time  a  detoxifying  action  in  the  blood. 

The  third  and  most  generally  accepted  theory  is  that  of  Wolff- 
Eisner.  He  bases  his  theory  on  the  fact  that  all  foreign  albumins 
introduced  into  the  tissues  are  dealt  with  by  the  production  of  specific 
antibodies — such  as  lysins  and  agglutinins.  He  therefore  assumes  that 
tuberculin  is  an  albumin  of  low  toxicity,  and  requires  breaking  down 
into  bodies  of  less  complex  constitution,  one  at  least  of  which  is  highly 
toxic,  before  any  toxic  action  is  noticeable. 

Sensitive  tissues,  i.  e.  those  of  an  infected  individual,  differ  from 
insensitive  tissues,  i.  e.  those  of  a  healthy  individual,  in  that  the  former 
contain  this  tuberculo-lysin  and  the  latter  do  not.  As  an  important 
adjunct  to  this  thecry,  Wolff-Eisner  considers  that  the  cells  of  the 


212  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

infected  individual  have  acquired  a  hypersensitiveness  to  the  foreign 
albumin  of  the  tubercle  bacilli,  comparable  to  the  hypersensitiveness 
to  tetano-toxin  evidenced  by  horses  which  have  been  immunised  against 
tetanus. 

This  theor}^  is  the  simplest  and  most  satisfactory  yet  advanced,  but 
Wolff-Eisner  has  not  yet  himself  adequately  explained  the  production 
of  focal  reactions.  The  theory  may,  however,  be  modified  and  extended 
as  follows,  and  made  to  explain  similar  phenomena  encountered  in  the 
therapeutic  use  of  all  vaccines. 

Tubercle  bacilli  and  tuberculin  and  other  bacteria  in  such  doses  as 
are  administered  are  practically  devoid  of  toxicity ;  they  excite  the 
production  of  the  corresponding  lysin,  which  breaks  them  down  and 
forms  a  toxic  decomposition  product.  This  lysin  we  know  is  formed 
rapidly  and  in  an  amount  far  in  excess  of  that  required  to  lysinise  the 
few  bacteria  contained  in  the  inoculum  ;  it  is  rapidly  carried  all  over 
the  body  and  to  the  infected  foci,  where  it  lysinises  the  living  infective 
agents  and  liberates  fresh  toxin.  The  toxin  formed  from  the  inoculum 
may  suffice  to  produce  a  local  reaction,  but  it  is  insufficient  to  produce 
focal  and  general  disturbances,  as  must  surely  be  admitted  when  one 
considers  the  minuteness  of  the  total  albumin  content  of  a  therapeutic 
dose ;  the  toxin  liberated  at  the  infected  foci  may,  however,  suffice  to 
cause  both  focal  and  general  reactions.  A  focal  reaction  of  some  degree, 
however  slight,  is  inevitable ;  a  general  reaction  will  be  produced  only  ' 
if  the  amount  of  toxin  be  sufficient,  and  the  activity  with  which  the 
body  responds  to  it  by  forming  antitoxin  be  not  great.  It  is  thus  obvious 
that  the  focal  reaction,  though  certainly  present,  may  escape  detection, 
because  the  induced  effects  of  the  toxin  may  be  too  slight  or  ill-adapted 
to  detection  by  means  of  the  stethoscope,  and  that,  on  the  other  hand,  * 
a  general  reaction  may  be  too  slight  for  observation,  owing  either  to  the 
small  amount  of  toxin  carried  into  the  circulation  and  so  to  the  nerve 
centres  from  the  infected  foci,  or  from  its  rapid  neutralisation  by  anti- 
toxin formed  by  the  tissues  in  response  to  the  elaboration  of  toxin. 

The  stimuli  brought  to  bear  on  the  tissue-cell^  by  the  toxin  may  be 
slight  and  exercise  a  stimulating  effect,  so  that  the  cells  respond  with 
extra  readiness  to  fresh  toxin,  i.  e.  they  may  be  rendered  hypersensitive, 
or  they  may  be  of  such  magnitude  that  they  exercise  a  poisoning,  or 
rather,  paralysing  effect,  and  so  induce  tolerance  to  the  poison. 

This  theory,  as  I  have  elaborated  it,  is  simple,  in  accord  with 
physiological  and  bio- chemical  facts,  and  seems  to  offer  a  full  and 
reasonable  explanation  of  all  points  of  difficulty. 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  213 

The  Diagnostic  Value  of  the  Subcutaneous  Test. 

The  subcutaneous  test  is  especially  to  be  employed  when  it  is 
necessary  either  to  make  an  early  diagnosis  in  doubtful  cases,  or  to 
decide  the  course  of  treatment  in  cases  where  there  is  difficulty  in 
arriving  at  a  differential  diagnosis.  If  the  test  be  conducted 
according  to  the  lines  I  have  laid  down  and  careful  watch  be 
kept  for  a  local  as  well  as  for  a  general  reaction  it  is  devoid  of  all 
danger;  a  little  extra  care  will  enable  the  general  practitioner  to 
utilise  it  with  a  freedom  equal  to  that  applicable  to  the  case  of 
the  specialist.  As  we  have  seen,  the  cutaneous,  percutaneous  and 
conjunctival  tests  give  indication  of  anatomical  as  well  as  of  clinical 
tuberculosis,  and  their  practical  utiHty  is  greatly  hmited  thereby.  If 
by  means  of  the  subcutaneous  test  a  focal  reaction  is  produced, 
ample  evidence  is  afforded  of  the  presence  of  active,  or,  at  least,  of 
incompletely  healed  tuberculosis.  That  mild,  general  reactions  may 
be  evidenced  in  cases  of  latent  and  of  healed  or  anatomical  tubercu- 
losis is  true,  but  the  percentage  of  cases  in  which  this  occurs  is 
decidedly  less  than  with  the  tests  already  described. 

A  positive  reaction,  focal  or  general,  sometimes  fails  to  appear  in 
slight  inactive  cases  where  the  disease  has  become  stationary,  and  also 
in  very  advanced  and  cachectic  cases. 

In  briefly  summarising  the  value  of  specific  products  in  the 
diagnosis  of  tuberculosis,  I  cannot  do  better  than  quote  the  opinions 
of  Bandelier  and  Roepke,  Vv^ith  whom  I  am  in  complete  accord  :  "'In 
the  early  diagnosis  of  pulmonary  tuberculosis  no  crucial  significance 
can  be  admitted  for  the  local  reaction  methods.  On  the  other  hand, 
no  objection  can  be  raised  to  the  employment  of  them,  singly  or  in 
combination,  before  the  subcutaneous  test,  on  account  of  their  simplicity 
and  the  obvious  advantages  they  possess  in  the  presence  of  fever  and 
other  troublesome  general  symptoms.  But  their  disadvantages  must 
not  be  lost  sight  of,  especially  their  uncertainty.  If  both  cutaneous 
and  conjunctival  tests  are  positive,  then  tuberculosis  may  be  decided 
upon  without  an}^  indication  of  its  site  or  character.  Is  one  or  both 
negative,  the  absence  of  a  tubercular  focus  is  not  demonstrated;  on  the 
contrary,  it  must  again  be  emphasised  that  both  methods  may  fail  in 
spite  of  active  pulmonary  tuberculosis  being  present.  In  all  these 
cases  the  subcutaneous  method  has  finally  to  decide  whether  tubercular 
disease  is  present  or  not.  It  is  still  par  excellence  the  diagnostic  agent 
for  the  detection  of  early  pulmonary  tuberculosis  in  adults.  Its  value 
is  increased  by  the  fact  that  in  a  high  percentage  of  subcutaneous  tests 
focal  reactions  make  their  appearance  and  allow  a  conclusion  as  to  the 
site  of  the  tuberculosis  in  the  lung."   And  again  :   '■'  The  value  of  tuber- 


2  14  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

culin  in  diagnosis  is  well  established.  The^  individual  methods  have 
their  special  advantages  and  disadvantages.  For  each  particular  case, 
to  make  use  of  the  advantages  and  exclude  the  disadvantages  is  the 
task  of  an  individualising  diagnostic  method.  In  diagnostic  certitude 
the  subcutaneous  test  stands  first ;  for  prognosis  all  methods  are 
equally  futile.  Tuberculin  diagnosis  may  be  introduced  into  general 
practice  without  impairing  the  results.  Ill-effects  to  the  patient  may 
with  certainty  be  avoided  by  proper  selection  of  cases  and  conscien- 
tious attention  to  details.  Tuberculin,  by  making  early  diagnosis 
possible,  is  destined  to  be  of  service  in  the  efficient  prophylaxis  and 
treatment  of  tuberculosis." 


Opsonic  Index  Estimations  in  Diagnosis. 

In  the  performance  of  this  test  the  introduction  of  the  specific 
products  may  be  from  without,  or  it  may  be  from  within,  the 
inoculations  then  occurring  at  the  infected  foci  either  from  spon- 
taneous or  induced  auto  -  inoculations.  This  test,  which  once 
enjoyed  a  considerable  vogue  in  England,  fell  into  desuetude 
and  neglect,  owing  partly  to  lack  of  care  on  the  part  of  many  in 
performing  the  estimation,  partly  to  ignorance  of  all  the  possible  causes 
of  fallacy.  It  is  now  being  revived,  and  promises  to  occupy  a  position 
of  deserved  esteem.  For  an  account  of  the  many  necessary  precautions 
which  must  be  taken  in  order  to  assure  a  reliable  result,  the  reader  is 
referred  to  a  paper  by  Colebrook  on  "  The  Opsonic  Method  in  Relation 
to  Tuberculosis "  {Practitioner,  January,  1913,  p.  138).  The  test 
depends  upon  these  observations  :  (i)  That  the  opsonic  index  of  the 
serum  of  the  healthy  individual  towards  the  tubercle  bacillus  lies  between 
the  limits  o"8  and  i'2,  and  usually  between  the  limits  0*9  and  I'l  ; 
(2)  that  the  opsonic  index  of  infected  individuals  tends  to  vary  from 
day  to  day,  so  that  on  occasions  it  may  diverge  considerably  from  these 
limits ;  (3)  that  the  opsonic  index  of  a  healthy  individual  is  little 
disturbed  by  the  administration  of  doses  of  tuberculin  below  "oooi  c.c. ; 
(4)  that  the  opsonic  index  of  an  infected  person  will  be  caused  to 
change  in  a  perfectly  definite'"manner  by  a  similar  administration.]^  ^^^ 

In  its  simplest  form  the  test  is  conducted  by  estimating  the  index 
of  the  individual  upon  several  different  occasions  when  he  is  pursuing 
his  normal  mode  of  living. 

In  a  more  definite  form  the  test  is  applied  by  first  keeping  the 
patient  at  rest,  and  then  making  him  auto-inoculate  himself  with  his 
own  tuberculin  either  by  the  performance  of  deep  breathing,  climbing 
upstairs  or  up  a  hill,  or  by  some  other  form  of  active  exercise. 
Specimens    of  blood    are    taken   just    before    the    exercise    is    begun, 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  2  I  5 

and  at  intervals  of  i,  3,  6,  12,  and  24  hours  thereafter  and  the 
indices  estimated.  If  considerable  fluctuations  are  observed  auto- 
inoculation  with  tuberculin  derived  from  his  own  bacilli  is  indicated, 
and  active  tuberculosis  is  almost  certainly  proved  to  be  present. 

If  no  signs  of  auto-inoculating  processes  are  thereby  indicated  a 
dose  of  "oooi  c.c.  of  old  tuberculin  or  of  T.R.  may  be  given.  Numerous 
experiments  have  shown  that  the  effect  of  this  upon  a  healthy 
individual  is  to  produce  a  lowering  of  the  index  perhaps  for  a  day  of 
not  more  than  a  decimal  point,  and  that  this  is  succeeded  by  a  short 
corresponding  elevation.  In  the  infected  individual  the  effect  is  much 
more  marked  ;  a  depression  of  two  or  three  decimal  points  may  result, 
and  not  pass  off  for  one  or  several  days,  and  is  succeeded  by  a  marked 
elevation,  which  falls  only  gradually  and  slowly. 

Provided  that  the  various  observations  are  carried  out  by  an  expert 
in  opsonic  index  estimations,  who  is  in  constant  practice  and  is 
conversant  with  all  the  various  possible  fallacies  and  disturbing 
influences,  an  indication  is  obtained  which  is  of  the  very  greatest 
service  as  a  diagnostic  aid.  In  delicacy  and  accuracy  the  method  often 
excels  all  others,  the  subcutaneous'  test  included,  and  it  has  the 
cardinal  advantage  of  revealing  the  presence  of  active  tuberculosis 
only.  The  great  drawbacks  lie  in  the  limited  number  of  dependable 
experts  in  index  observations  available  and  in  the  considerable  expense 
which  must  necessarily  be  incurred.  Not  only  is  it  capable  of  affording 
great  help  in  the  early  diagnosis  of  tuberculosis,  but  also  of  enabling 
the  determination  to  be  made  with  considerable  accuracy  as  to  when 
all  active  processes  of  disease  are  in  abeyance. 

Classification  of  Cases  of  Pulmonary  Tuberculosis. 

From  the  point  of  view  of  tuberculin  therapy  the  classification  of  cases 
of  pulmonary  tuberculosis  according  to  the  extent  and  distribution  of  the 
lesions,  as  in  Turban's  classification,  is  of  no  particular  significance.  Of 
much  greater  importanceis  the  natureoftheprocessesat  the  foci  of  disease 
and  the  manner  in  which  the  body  is  making  response  to  the  infection. 
For  instance,  the  prognosis  in  even  a  very  early  case  of  miliary  tuber- 
culosis is  much  less  favourable  than  that  of  an  acute  pneumonic  tuber- 
culosis of  a  single  lobe,  and  that  of  the  latter  less  favourable  than  that 
of  a  fibro-caseous  involvement  of  more  than  one  lobe. 

Tuberculin  is  not  directly  a  curative  agent  in  the  sense  that  anti- 
diphtheritic  serum  is,  it  is  merely  an  active  immunising  agent,  a  stimu- 
lant for  the  tissue-cells  of  the  formation  of  specific  antibodies.  It 
therefore  follows  that  the  tissue-cells  must  be  in  a  condition  which 
enables    them    to    respond   to    the    stimuli    and    elaborate  the  neces- 


2l6  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

sary  antibodies.  The  period  of  disease  at  which  the  body  can  best  per- 
form this  task  is,  as  Koch  so  strongly  urged,  in  the  early  stages  of  a 
strictly  localised  infection.  In  the  earliest  stages  of  miliary  tubercu- 
losis Koch  detected  a  definite  attempt  on  the  part  of  the  body  to 
elaborate  specific  antibodies,  but  this  power  is  soon  lost  and  the  cells 
can  no  longer  respond  to  stimulation,  as  is  clearly  shown  by  their 
failure  to  react  to  the  various  diagnostic  tests.  For  a  similar  reason 
in  cases  of  advanced  cachexia  tuberculin  is  of  no  avail. 

]ylany  authorities  would  restrict  the  use  of  tuberculin  to  uncompli- 
cated afebrile  cases  in  Stages  I  and  II  of  Turban,  i.  e.  to  cases  whose 
temperature  does  not  rise  above  gg°  F.,  in  which  cavitation  has  not  yet 
occurred,  and  where  the  process  is  confined  to  not  more  than  two  lobes. 
Others  would  exclude  all  cases  in  which  mixed  infection  is  present,  but 
fail  to  realise  that  mixed  infection  is  almost  certainly  present  in  all 
cases  of  open  tuberculosis,  and  inasmuch  as  they  administer  the  drug 
to  many  such  cases  obviously  fail  to  observe  their  own  dictum.  Mixed 
infection,  per  se,  is  no  contra-indication  to  the  use  of  tuberculin,  but,  as 
we  have  seen  in  Chapter  X,  so  complicates  the  control  of  dosage  and 
intervals  by  obscuring  the  focal  and  general  reaction  thereto  that  the 
difficulty  of  administration  is  immensely  increased. 

Actively  progressive  forms  of  the  disease  are  not  likely  to  be  bene- 
fited, but  advanced  forms  where  much  destruction  has  occurred  may 
recover,  provided  the  destruction  falls  somewhat  short  of  that  degree 
in  which  pathological  anatomy  shows  that  spontaneous  cure  or  arrest 
may  take  place.  The  best  method  of  classification  is  that  based  upon 
a  consideration  of  the  nature  of  the  processes  which  are  occurring  at 
the  foci  of  disease  and  of  the  manner  in  which  the  body  is  responding 
to  the  infection  ;  such  an  one  is  that  proposed  by  Inman,  who  divides 
cases  into  the  following  three  classes : 

Class  I  :  Resting  febrile,  i.  e.  those  which  show  a  temperature  of 
99°  F.  or  over  when  at  rest  in  bed. 

Class  II:  Ambulant  febrile,  resting  afebrile,  i.e.  those  which 
remain  afebrile  so  long  as  they  are  at  absolute  rest,  but  become  febrile 
when  allowed  to  get  up  and  take  exercise.  Class  II  is  often  a  transi- 
tion between  Classes  I  and  III. 

Class  III :  Ambulant  afebrile,  i.  e.  those  without  fever  in  spite  of 
exercise  or  work. 

The  febrility  of  tuberculosis  is,  as  Inman  and  Paterson  have  shown, 
due  to  auto-inoculations  with  specific  products  from  the  bacilli  at  the 
foci  of  disease,  but  it  is  necessary  to  take  a  somewhat  wider  view  of 
what  constitutes  the  auto-inoculations  than  is  done  by  these  observers. 
They  appear  to  regard  them  as  being  composed  of  the  products  of 
the   tubercle    bacilli    alone,  whereas  in  many  cases  they  also  consist 


THE    BACTERIAL    DISEASES    OF    RESPIRATIOX.  2  1/ 

of  the  products  of  the  bacilli  which  constitute  the  mixed  infection. 
Repeatedly  one  sees  a  case  of  "'  ambulant  afebrile "  tuberculosis 
suddenly  become  "'ambulant  febrile,''  and  probably  even  •"'resting 
febrile."  I  have  carefully  examined  several  such  cases,  and  have  in 
every  instance  found  that  the  factor  at  work  was  a  fresh  invasion  by 
other  than  the  tubercle  bacilli.  I  do  not  mean  to  conve}'  that  this 
always  is  the  case,  and  that  exacerbation  of  the  tuberculous  infection  is 
never  responsible  for  the  change  of  type,  for  of  course  it  is.  As  a  rule, 
however,  the  following  distinction  holds  :  In  ■'"'  ambulant  afebrile  "  cases 
w^hich  suddenly  become  "resting  febrile,"  the  factor  usually  is  the 
access  of  mixed  infection,  whereas,  when  they  become  •'■'  ambulant 
febrile,"'  but  '■' resting  afebrile."  the  factor  usually  is  exacerbation  of  the 
tuberculous  process. 

The  researches  of  Inman  and  Paterson  have  shown  that  in  the 
resting  febrile  cases  of  Class  I  the  stimuli  are  excessive  and  irregular, 
and  tend  to  overtax  the  mechanism  of  immunity,  and  that  unless  these 
stimuli  can  be  controlled  by  absolute  or  "''typhoid"'  rest  the  course 
is  inevitably  downhill,  whereas  in  the  ambulant  febrile  but  resting 
afebrile  cases  of  Class  II  the  stimuli  are  adequate  and  controllable,  and 
such  cases  tend  to  get  well ;  while,  hnally,  in  the  ambulant  afebrile 
cases  of  Class  III  the  stimuli  are  insufncient  and  the  tendency  is  towards 
little  activity  and  chronicity.  Bv  absolute  or  "typhoid  "  rest  they  have 
shown  that  cases  of  Class  I  may  sometimes  have  their  stimuli 
reduced  and  controlled,  and  so  they  may  be  brought  into  Class  II  or  III. 

Cases  of  Class  II  may  become  cured  if  the  stimuli  be  adequately 
maintained  for  a  sufficiently  long  time,  but  the\-  tend  to  gravitate  into 
Class  III,  or  into  Class  I,  if  a  sudden  exacerbation  of  the  tuberculous 
process  occur  or  a  mixed  infection  be  superadded. 

Class  III  comprises  the  chronic  cases  with  long  periods  of  latency 
and  inactivity,  alternating  with  occasional  relapses. 

These  considerations  considerably  facilitate  the  selection  of  cases 
suitable  for  tuberculin  treatment,  and  also  indicate  the  proper  time  for 
its  inception.  Thus  all  ambulant  afebrile  cases  are  suitable  for  the 
administration  of  tuberculin ;  many  will  perhaps  get  \^'ell  without 
specific  medication,  but  experience  tends  to  show  clearly  that  tuberculin 
properly  administered  will  markedh'  increase  the  ratios  of  recoveries 
and  will  do  no  apparent  harm  in  an}-  instance. 

In  the  ambulant  febrile  and  resting  afebrile  cases  the  immunising 
impulses  can  be  controlled  by  carefully  graduated  rest  and  exercise,  and 
if  this  be  done  and  the  best  hygienic  conditions  be  maintained  the 
tendency  is  towards  recovery.  A  necessary  sequel  to  this  is  that 
sooner  or  later  such  cases  must  pass  into  the  categon.'  of  the  "ambulant 
afebrile,"    v/here,    as   we   have    seen,    the    stimuli    tend    to     become 


2l8  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

inadequate.     On   the  other  hand,  a  certain   percentage  of  the  cases 
of  Class  II  tend  to  gravitate  into  Class  I,  and  so  towards  a  fatal  issue. 

It  therefore  follows  that  inasmuch  as  tuberculin  induces  a  curative 
effect,  its  application  in  cases  of  Class  II  will  tend  to  expedite  the 
recovery  of  such  cases  as  gravitate  into  Class  III,  and  will  diminish 
the  proportion  of  cases  which  tend  to  gravitate  into  Class  I.  Practical 
experience  shows  that  these  anticipations  are  fulfilled.  Cases  of  early 
tuberculosis  almost  always  fall  into  this  category,  and  were  considered 
by  Koch  to  be  those  to  whom  tuberculin  was  especially  likely  to  prove 
beneficial.  But,  it  may  well  be  urged,  why  interfere  with  cases  that 
are  obviously  improving  ?  This  is  a  perfectly  valid  objection,  but 
experience  has  shown  that  tuberculin  properly  administered  is  devoid 
of  harm,  and  may  be  productive  of  good  even  in  the  most  rapidly 
improving  cases.  Its  administration  also  has  the  advantage  that  it 
necessitates  the  patient  being  kept  under  close  observation,  and  so 
facilitates  the  early  detection  of  any  unfavourable  tendency.  If  the 
preference,  however,  is  for  the  treatment  of  these  cases  on  non-specific 
lines,  it  then  becomes  incumbent  to  maintain  an  especially  close  watch 
upon  the  patient,  with  a  view,  on  the  one  hand,  to  increasing  the 
immunising  impulses  when  the}^  tend  to  weaken^  and,  on  the  other 
hand,  to  controlling  the  impulses  when  they  tend  to  become  excessive 
and  irregular. 

It  remains  now  to  consider  whether  tuberculin  treatment  is  appli- 
cable to  any  cases  belonging  to  Class  I.  As  we  have  already  seen, 
the  temperature  of  all  three  classes  is  due  either  in  whole  or  part  to 
the  action  of  tuberculo-toxin  reaching  the  central  nervous  system  from 
the  foci  of  disease ;  in  cases  of  Class  I  it  is  especially  important  to 
ascertain  whether  the  pyrexia  is  due,  entirely  or  only  in  part,  to  this 
influence.  The  other  possibility  is  the  presence  of  mixed  infection, 
which  is  also  by  no  means  excluded  as  a  factor  in  cases  belonging 
to  Classes  II  and  III.  This  question  of  mixed  infection  has  been  fully 
dealt  with  in  Chapter  X,  where  full  particulars  have  been  given  for  its 
detection  and  treatment.  The  prime  consideration,  therefore,  in  the 
treatment  of  cases  belonging  to  Class  I  is  the  determination  as  to 
whether  the  pyrexia  is  due  to  the  tubercular  infection  alone  or  to 
mixed  infection  as  well.  If  mixed  infection  be  an  important  factor, 
treatment  with  the  appropriate  vaccines  will  probably  settle  this 
question  and  assist  in  bringing  these  cases  into  the  category  of 
Class  II,  when  tuberculin  treatment  may  be  considered. 

If  the  influence  of  mixed  infection  is  disproved,  the  question  has  to 
be  considered  whether  tuberculin  will  afford  material  help.  Theo- 
retically it  would  appear  unlikely  that  the  administration  of  further 
stimuli  could  assist  in  the  control  of  excessive  and  ill-ordered  stimuli. 


THE    BACTERIAL   DISEASES    OF    RESPIRATION.  219 

and  clinical  experience  tends  to  confirm  this  view.  In  a  small  per- 
centage of  cases  it  is,  however,  found  that  minimal  doses  of  tuberculin  do 
assist  in  the  raising  of  toxin  immunity.  If  absolute  or  "typhoid"  rest 
fail  to  influence  the  pyrexia  of  these  cases,  the  issue  is  practically 
certain  to  be  a  fatal  one,  and  it  is  therefore  justifiable,  after  explaining 
the  state  of  affairs  to  the  patient,  to  make  a  last  endeavour  to  influence 
the  course  of  the  disease  for  good.  Cure  may  be  a  very  remote 
prospect,  but  increase  of  comfort  may  be  brought  about  and  the 
ultimate  end  may  be  postponed.  Any  active  interference  must,  how- 
ever, be  conducted  with  extreme  care,  or  the  effect  may  be  the  reverse 
of  that  intended. 

Finalty",  a  few  words  must  be  said  as  regards  the  question  of  when 
to  b?>gin  tuberculin  treatment  in  cases  which  are  suitable  for  this 
procedure.  The  usual  answer  given  is — "  As  soon  as  possible. '^  Person- 
ally I  think  this  needs  some  qualification.  Cases  with  mixed  infection 
are  not  necessarily  to  be  excluded  from  treatment,  and,  indeed,  most 
observers  frequently  treat  such  cases  with  tuberculin,  failing  to  recog- 
nise that  mixed  infection  is  really  present ;  in  these  it  is  not  wise  to 
combine  vaccine  and  tuberculin  treatment,  for  the  effect  of  each  is 
likely  to  mask  the  effect  of  the  other.  I  think  I  have  amply  demon- 
strated in  Chapter  X  that  the  wiser  course  is  to  deal  first  with  the 
mixed  infection  and  then  with  the  tuberculous  process,  so  that  I  think 
the  proper  answer  to  the  question  is  "  as  soon  as  possible  after  any 
mixed  infection  present  has  been  adequately  dealt  with." 

Tlic   Choice  of  Tuberculin. 

As  a  necessary  preliminary  to  the  consideration  of  this  question 
it  is  well  to  recapitulate  a  few  important  points. 

Firstly,  that  tuberculin  is  an  actively  immunising  substance ;  it 
contains  albumins  constituting  the  toxic  elements  formed  by  the 
bacterial  growth,  as  well  as  those  constituting  the  essential  proto- 
plasmic substance  of  the  bacilli. 

Some  of  the  tuberculins  contain  only  one  or  other  of  these  bodies, 
some  contain  both. 

The  human  tissues  are  capable  of  elaborating  antibodies  to  these 
albumins,  so  that  immunity  can  be  excited  both  against  the  toxins  and 
the  bacilli  themselves.  Of  these  antibodies  little  is  known,  but  among 
them  lysin,  agglutinin,  opsonin,  antituberculin  and  possibly  antitoxin 
may  be  mentioned. 

In  cases  of  pulmonary  tuberculosis  the  general  symptoms  are  due 
to  the  action  of  a  toxic  component  of  lysinised  tuberculin  upon  the 
central  nervous  system,  the  focal  changes  are  due  chiefly  to  secreted 


2  20  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

endotoxins^  the  range  of  their  activities  being  more  or  less  confined  to 
the  infected  areas.  The  true  ultimate  objective  of  treatment  is  to  bring 
about  extinction  of  the  infection,  but  the  production  of  bactericidal 
effects  is  complicated  by  the  existence  of  a  peculiar  sensitiveness  of  the 
tissues  to  lysinised  tuberculin,  and  the  consequent  necessity  of  establish- 
ing a  high  degree  of  tolerance  to  the  toxin.  When  general  symptoms  are 
little  marked  these  difficulties  are  minimal,  but  when  constitutional 
disturbances  are  severe  or  easily  excited  it  is  necessary  that  attention 
should  be  directed  to  the  establishment  of  a  high  degree  of  tolerance. 

The  statem.ent  is  often  made  that  all  the  varieties  of  tuberculin  are 
capable  of  producing  the  same  results,  the  only  difference  being  that 
some  are  more  powerful  agents  than  others.  But  with  this  I  do  not 
absolutely  agree  :  there  is,  and  must  be^  a  difference  in  the  immune 
bodies  which  they  are  capable  of  inciting  corresponding  to  the  differ- 
ence of  their  constitution.  Thus  T.R.,  and  to  a  less  degree  B.E.,  will 
lead  more  especially  to  the  production  of  antibodies  to  the  proto- 
plasmic albumin  ;  T.O-xA..,  and  old  tuberculin,  on  the  other  hand,  will 
incite  the  production  of  antibodies  more  especially  to  the  soluble  toxins, 
and  so  will  the  more  powerfully  stimulate  the  development  of  toler- 
ance. 

While  old  tuberculin  is  absorbed  with  considerable  rapidity,  B.E. 
is  absorbed  very  slowly  ;  the  production  of  antibodies  is  correspondingly 
affected,  and  it  therefore  follows  that  in  febrile  and  highh'  sensitive 
cases  B.E.  is  less  likely  to  lead  to  violent  reactions  than  is  old  tuber- 
culin, and  this  preparation  is  therefore  preferred  for  use  at  the  begin- 
ning of  the  treatment  of  such  cases. 

Sahli  and  others  state  that  of  all  tuberculins  Beraneck's  contains 
the  least  amount  of  non-specific  toxins,  and  at  the  same  time  a  high 
content  of  specific  toxin  and  essential  protoplasmic  albumin  ;  they 
therefore  consider  it  to  be  the  best  preparation  for  general  use. 

The  preparations  derived  from  the  bovine  strain  of  bacilli  probably 
differ  from  those  derived  from  the  human  strain  mainly  in  the  direction 
of  being  much  milder  in  their  actions,  and  therefore  less  liable  to 
produce  severe  disturbances. 

Although  it  is  not  possible  to  give  definite  values  for  the  immunising 
powers  of  the  various  tuberculins,  it  is  possible  to  arrange  them 
roughly  as  follows  in  descending  order,  the  attached  numerals  being 
an  approximate  value  of  their  respective  strengths  :  Denys'  B.F.  (500), 
T.  (200),  P.T.  (40),  B.E.  and  T.R.  (5),  and  P.T.O.  (i). 

Until  one  has  had  a  fair  amount  of  experience  of  tuberculin  therapy, 
it  is  well  to  restrict  oneself  to  the  use  of  a  few  preparations  only ;  for 
most  purposes  old  tuberculin,  or  T.,  will  serve  well,  and  it  is  perhaps 
advisable  to  employ  this  preparation  alone  till  considerable  practice  has 


THE    BACTERIAL    DISEASES    OF    RESPIRATION.  22  1 

brought  familiarity  with  dosage,  and  the  various  \va3-3  in  which  the 
human  tissues  react  thereto.  In  dispensary  work  and  the  treatment  of 
ambulant  cases  the  use  of  P.T.O.,  P.T.,  and  T.  in  sequence  has  much 
to  recommend  it,  the  slight  toxicity  of  the  first  preparation  minimising 
the  risk  of  exciting  undesirable  reactions. 

Personally,  I  think  that  in  every  instance  treatment  should  be  con- 
cluded by  a  course  of  bacillar}'  emulsion,  a  two-fold  reason  for  this 
existing  in  the  facts — (i)  that  this  preparation  is  a  whole  bacillar\- 
product.  and  is  therefore  best  suited  for  the  production  of  anti-bacterial 
immunity,  and  (2)  its  rate  of  absorption  being  slow  the  immunity  which 
has  been  established  is  thereby  maintained  at  a  high  level  for  a  con- 
siderable period.  As  transition  is  made  from  one  tuberculin  to  another, 
it  is  necessary  to  keep  in  mind  the  approximate  relative  strengths  of 
the  respecti^"e  preparations  ;  for  instance,  if  the  dosage  of  P.T.O.  has 
been  raised  to  o'l  c.c,  and  it  is  thought  advisable  to  make  substitution 
of  P.T.,  it  will  not  be  good  practice  to  begin  with  a  minimal  dose  such 
as  "ooooi  c.c,  for  thereby  time  will  be  lost  and  opportunity  also  given 
for  tolerance  to  drop  from  that  high  level  to  which  it  has  been  raised 
with  so  much  care.  The  dose  of  P.T.  corresponding  to  O'l  c.c.  of  P.T.O. 
being  about  '^  c.c.  or  '0025  c.c,  there  will  be  little  danger  in  beginning 
with  a  dose  of  "0005  c.c.  of  P.T.  A  similar  calculation  will  give  the 
appropriate  initial  dose  of  other  preparations  as  they  are  substituted  in 
turn.  Personally,  in  making  transition,  I  prefer  to  begin  with  onh' 
one-fifth  of  the  calculated  dosages. 

Conduct  of  the  Course  of  Treatment :  Dosage  and  Intervals. 

The  procedures  which  have  been  devised  for  the  administration  of 
tuberculin  are  almost  as  many  in  number  as  are  the  specialists  in  the 
use  of  the  drug.  It  is  quite  impossible  to  enter  into  a  discussion  of  the 
merits  and  demerits  of  each,  and  I  propose  to  give  onlv  such  general 
instructions  as  experience  has  shown  to  be  applicable  to  the  great 
majority  of  cases,  and  to  point  out  how  these  may  require  modification 
to  suit  individual  cases,  for  let  me  once  more  emphasise  the  fact  that 
in  tuberculosis,  more  than  in  any  other  disease,  it  is  necessar_v  to  pay 
the  most  strict  attention  to  the  peculiarities  of  each  individual  case, 
and  that  it  is  only  by  doing  this  that  the  incidental  dangers  can  be 
avoided  and  the  best  results  secured. 

While  it  must  be  admitted  that  the  establishment  of  a  high  degree 
of  tolerance  of  the  tissues  to  tuberculo-toxin  is  a  very  important  essen- 
tial, inasmuch  as  it  is  only  by  the  achievement  of  this  end  that  the 
grave  constitutional  disturbances  due  to  intolerance  of  the  toxin  can 
be  removed  and  kept  in  abeyance,  I  would  join  serious  issue  with  all 
those  who  make  this  the  sole  objective  of  their  treatment,  and  assume 


2  22  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

that  high  tolerance  and  extinction  of  infection  go  hand  in  hand,  and 
are  necessarily  the  same  thing.  The  true  aim  of  all  treatment  should 
be  the  extinction  of  the  infection,  and  the  best  indication  of  progress 
in  this  direction  is  the  condition  of  the  local  lesions.  Now,  observa- 
tions of  pulse  and  temperature  and  the  general  condition  of  the 
patient  are  easy,  and  are  carried  out  as  a  mere  routine  in  the  treatment 
of  all  severe  forms  of  bacterial  infection,  but  however  valuable  they 
may  be  in  themselves  they  do  not  necessarily  afford  a  good  indication 
of  the  condition  of  the  local  lesions,  and  this  contention  holds  with 
especial  force  in  regard  to  pulmonary  tuberculosis.  No  sound  observer 
would  be  content  to  treat  a  case  of  tuberculous  laryngitis  without 
making  close  scrutiny  of  the  progress  of  the  lesion,  nor  be  satisfied 
that  all  was  going  well  with  a  case  of  pneumonia  without  carefully 
examining  the  chest,  yet  many,  if  not  most,  authorities  advise  the 
control  of  tuberculin  therapy  by  means  of  pulse,  temperature,  and 
general  condition,  to  the  neglect  of  careful  observation  of  the  chest. 
For  this  two  things  must  be  held  responsible  :  firstly,  disinclination  or 
inability  to  devote  the  time  to  careful  systematic  stethoscopic  observa- 
tions ;  secondly,  the  entirely  fallacious  view  already  mentioned  as  held 
by  many,  that  a  general  reaction  can  be  elicited  in  the  absence  of  a 
focal  one,  T  have  already  mentioned  the  production  of  the  former  is 
dependent  upon  the  production  of  the  latter,  for  the  amount  of  toxin 
that  can  be  formed  by  the  tuberculo-lysin  from  any  but  the  largest 
therapeutic  doses  of  tuberculin  falls  far  below  that  necessary  for  the 
poisoning  of  the  central  nervous  system  upon  which  constitutional 
symptoms  depend  ;  the  local  reaction  maybe  so  produced,  but  the  focal 
and  general  reactions  are  dependent  upon  the  increased  elaboration  of 
antibodies  set  up  by  the  inoculation,  and  the  action  of  these  upon  the 
innumerable  bacilli  at  the  foci  of  infection.  It  is  a  matter  of  common 
observation  that  marked  focal  changes  can  be  detected  in  cases  of 
lupus,  tuberculous  laryngitis  and  iritis  after  such  a  dose  of  tuberculin 
as  fails  to  produce  the  least  constitutional  disturbances,  and  it  is  only 
the  lack  of  careful  stethoscopic  observations  at  suitable  intervals  that 
has  given  rise  to  this  prevalent  fallacy.  Occasionally,  of  course,  lesions 
may  be  deep-seated  in  the  lung,  or  be  productive  of  few  signs  discover- 
able by  the  stethoscope,  but  a  considerable  experience  enables  me  to 
affirm  that  such  cases  are  clinically  rare  ;  I  have  never  yet  seen  a  case 
in  which  alterations,  at  all  events  in  breath-sounds,  were  not  produced 
by  a  therapeutic  dose  of  tuberculin  which  sufficed  to  produce  even  the 
mildest  constitutional  disturbance.  Such  cases  may,  however,  exist, 
and  there  are  others  where  intolerance  is  very  marked  relatively  to  the 
focal  reactions,  and  it  is  only  in  these,  and  in, cases  where  opportunities 
cannot  be  afforded  for  close  clinical  observations,  that  the  guidance 


THE    J3ACTERIAL    DISEASES    OF    RESPIRATION.  223 

of  the  general  reaction  should  be    substituted  for   that    of  the    focal 
reaction. 

The  best  procedure  of  all  obviously  is  that  wherein  due  regard  is 
paid  to  all  the  varying  aspects  of  the  case,  and  wherein  the  local,  focal, 
and  general  reactions  are  all  carefully  correlated  and  weighed  together. 

The  procedure  to  be  followed  in  the  stethoscopy  of  the  chest  after 
the  administration  of  a  therapeutic  dose  of  tuberculin  is  precisely 
similar  to  that  which  has  already  been  so  fully  described  and  illustrated 
in  Chapter  X-,  pp.  155-170,  for  the  control  of  dosage  and  intervals  in 
the  treatment,  by  means  of  vaccines,  of  the  mixed  infection,  and  needs 
little  further  consideration. 

As  with  all  other  methods,  treatment  is  begun  with  such  a  minimal 
dose  of  the  selected  tuberculin  as  the  clinical  condition  of  the  patient 
and  other  considerations  indicate  ;  this,  for  most  cases,  may  be  'ooooi 
c.c.  of  either  P.T.O.,  T.R.  or  B.E,  -000005  P-T.,  "000002  T.,  'oooooi  T. 
Beraneck  ;  if  the  case  be  a  pyrexial  or  very  early  one  half  the  above 
dosages  may  be  employed.     If  the  patient  be  a  strong  healthy  subject 
or   the   disease  be   of  long   standing   and    few   symptoms,  the  above 
dosages  may   be  safely  increased  two-  or  even  live-fold,   but  inasmuch 
as  the  increase  of  dosage  is,  as  a  rule,  rapid,  there  is  little  occasion  for 
this.     If  neither  focal  nor  general  reaction  results,  the  initial  dosage  is 
doubled  in  three  days,  and  this  procedure  continued  until  one  or  other 
reaction  is  produced,  a  focal  one  being,  as  1  have  said,  almost  always 
discoverable  before  a  general  one.     As  soon   as  a  dosage  is  attained 
which  does  produce  a  reaction  a  slight  reconsideration   of  the  clinical 
features  of  the  case  is  necessary,  the  principles   of  tuberculin  -.therapy 
differing  slightly  from  those  of  other  forms  of  vaccine   therapy  in  that 
tolerance  has  to  be  taken  into  account  as  well  as  antibacterial  imm.u- 
nity.     Accordingly,  if  tolerance  is  low,  as  evidenced  by  slight  degrees 
of  exercise    causing  auto-inoculatory  phenomena,   it    is    desirable    to 
produce  a  rapid  increase  of  tolerance  ;  clinical  experience   has  shown 
that  this  can  only  be  done  by  giving  increased  dosages  at  short  intervals, 
viz.  of  about  three  to  five  days.     Under  these  circumstances  increased 
dosage  will  be  given  at  each  inoculation  provided  that  careful  observa- 
tion of  the  focal  reactions  show  that  these  are  not  being  unduly  excited, 
and  that  sufficient   time  is  allowed  to  lapse  between   inoculations  to 
permit  the  local  condition  deriving  full  benefit  from  the  focal  reaction  ; 
the  fulfilment  of  this  condition  usually  necessitates  a  slightly  longer 
period  being  allowed  between  inoculations  than  would  be  allowed  if  the 
raising  of  tolerance  were    the    sole    objective — in    other    words,   the 
intervals  may  have  to  be  five  to  seven  days  instead  of  three  to  five  days. 
On  the  other  hand,  if  tolerance  is  adequate,  as  shown  by  the  absence 
of  auto-inoculatory   phenomena,  the  necessity  for   rapid    increase    of 


2  24  THE    BACTERIAL   DISEASES    OF    RESPIRATION. 

dosage  does  not  exist,  and  so  long  as  a  certain  dosage  produces  a  satis- 
factory focal  reaction  there  is  no  need  to  go  beyond  it.  As  a  rule  it 
will  be  found  that  after  three  or  four  doses  of  a  given  magnitude 
focal  reaction  begins  to  fail  :  this  is  the  signal  for  immediate  increase 
of  dosage.  A  very  satisfactory  scale  for  dosage  is  that  employed  by 
Bandelier  and  Roepke,  viz.  i,  1*5,  2,  3,  5,  7,  10,  15,  20  and  so  on;  this 
will  serve  for  the  great  majority  of  cases,  but  will  need  modifying  to 
meet  individual  peculiarities. 

It  should  be  remembered  that  if  at  any  time  increased  dosage  produces 
an  excessive  reaction  or  undesirable  constitutional  effects  in  any  way, 
prolonged  rise  of  temperature  or  of  pulse-rate  and  loss  of  weight  being 
the  most  important  symptoms  under  this  category,  return  should  at 
once  be  made  to  that  dosage  which  failed  to  give  rise  to  these  ill- 
results,  and  any  subsequent  increase  is  to  be  made  with  especial  care 
and  caution. 

The  temperatures  which  should  be  taken  for  control  purposes  are 
best  determined  experimentally  for  every  case,  for  some  have  their 
highest  temperatures  at  one  hour  of  the  day,  others  at  a  totally  different 
hour.  Before  treatment  is  ever  begun  it  is  therefore  wise  to  send  the 
patient  to  bed,  in  order  that  rectal  temperatures  may  be  taken  every 
three  or  even  every  two  hours,  and  that  careful  clinical  study  may  be 
made  of  the  patient  as  an  individual.  Thereafter  it  will,  as  a  rule, 
suffice  to  take  the  temperature  at  such  times  as  correspond  to  the  usual 
daily  maximum  and  minimum,  and  if  there  is  any  great  objection  to  rectal 
temperatures,  mouth  temperatures,  or,  better,  those  taken  in  the  stream 
of  urine,  may  be  substituted.  During  the  twenty-four  hours  following 
an  inoculation  three-hourly  temperatures  are,  however,  most  desirable. 

Under  this  scheme  of  treatment  it  will  be  seen  that  primarily  atten- 
tion is  focussed  upon  the  changes  induced  at  the  foci  of  infection, 
secondarily  upon  the  general  reaction  and  constitutional  effects,  and 
thirdly  upon  all  the  signs  and  symptoms  that  can  give  any  indication 
of  the  progress  of  immunisation,  such  as  the  sputum,  urine,  appetite, 
body-weight  and  feeling  of  general  well-being. 

The  near  completion  of  a  course  of  treatment  is  indicated  by  : 

(i)  The  complete  disappearance  of  all  signs  and  symptoms  ; 

(2)  A  failure  to  incite  auto-inoculatory  phenomena  by  hard  exercise 
or  work  ;  and  perhaps — 

(3)  the  failure  of  such  dosages  as  o'l  to  o"2  c.c.  of  old  tuberculin, 
tuberculin  Beraneck,  or  Denys'  bouillon  filtre  to  produce  either  a  focal 
or  a  general  reaction. 

After  this  stage  has  been  reached  it  is  well  to  continue  treatment 
with  a  few  further  doses  of  the  patient's  optimal  maximum  strength, 
i.e.,  of  that  dosage  which  produces  the  best  clinical  results,  given  at 


THE    BACTERIAL   DISEASES    OF    RESPIRATION.  225 

lengthening  intervals  such  as  one  week,  two  weeks,  three  weeks,  and 
finally  one  month. 

No  matter  how  complete  a  cure  may  appear  to  be  it  is  highly 
desirable  that  the  patient  should  return  every  four  to  six  months  for 
careful  re-examination  of  the  chest  and  general  condition.  The  physi- 
cian should  then  also  determine  whether  auto-inoculation  can  be 
induced,  and  also  estimate  the  degree  of  tolerance  by  means  of  cutaneous 
tests  with  such  dilutions  of  tuberculin  as  5  per  cent.,  10  per  cent., 
25  per  cent.,  50  per  cent.,  and  100  per  cent.  Should  any  suspicion  of 
relapse  exist  a  fresh  course  of  immunisation  is  to  be  strongly  urged 
upon  the  patient. 

Difficulties  in  the  course  of  treatment  are  almost  sure  to  arise,  but 
the  number  and  magnitude  of  these  may  be  reduced  by  the  proper 
selection  of  cases.  They  arise  at  any  time — at  the  beginning,  near  the 
end,  or  in  the  middle  of  treatment. 

When  they  occur  at  the  beginning  they  are,  as  a  rule,  due  to  the 
high  reactivity  of  the  tissues  to  tuberculin,  i.e.  to  a  high  degree  of 
sensitiveness,  and  are  especially  liable  to  be  encountered  in  very  early 
cases  and  in  those  that  have  reacted  strongly  to  a  diagnostic  dose  of 
tuberculin.  In  one  instance,  a  very  early  case  indeed  reacted  to  a 
diagnostic  dose  of  "oooi  c.c.  of  old  tuberculin  in  a  very  violent  manner. 
After  two  months'  waiting  I  endeavoured  to  begin  tuberculin  treatment, 
but  doses  even  of  '000001  c.c.  of  P.T.  and  P.T.O.  induced  such  marked 
constitutional  upsets,  including  loss  of  weight  of  4^-1  lb.  per  week,  that  it 
was  thought  almost  hopeless  to  continue  specific  therapy  in-'the  face  of 
such  extreme  sensitiveness.  Difficulties  in  the  middle  of  treatment  are 
more  likely  to  arise  from  the  onset  of  mixed  infection  or  from  a  revival  or 
re-exacerbation  of  a  mixed  infection  which  prior  vaccine  treatment  had 
failed  to  eradicate  entirely  than  from  any  other  cause.  Sometimes  it  will 
originate  from  the  non-correspondence  of  the  optimal  therapeutic  dosage 
with  that  which  the  patient  can  then  tolerate ;  his  tissues  may  be  able 
to  tolerate  far  larger  doses  than  they  are  actually  receiving ;  general 
reactions  may  be  therefore  conspicuous  by  their  absence,  focal  reactions 
may  be  very  difficult  of  detection,  and  accordingly  the  limits  of  dosage 
best  suited  to  the  needs  of  the  patient  are  exceeded,  little  or  no  indica- 
tion being  given,  for  some  time  that  such  is  the  case.  The  clue  will 
usually  be  afforded  by  a  process  of  exclusion,  and  by  such  symptoms  as 
slight  loss  of  appetite  and  weight,  depression  and  feeling  of  not  being 
so  well  taking  the  place  of  previously  perfectly  satisfactory  ones,  and 
this  in  the  absence  of  any  unfavourable  signs  at  the  foci  of  infection. 
The  suspension  of  the  treatment  for  a  couple  of  weeks  and  resumption 
then  with  dosages  reduced  to  one  third  or  one  fourth  will  do  little 
harm  whenever  suspicion  exists  of  such  a  state  of  things^  and  may  be 
productive  of  much  good. 

15 


2  26  THE    BACTERIAL    DISEASES    OF    RESPIRATION. 

The  difficulties  which  may  arise  towards  the  end  of  treatment  are 
concerned  chiefly  with  the  determination  of  ultimate  dosage  and  the 
time  for  suspending  further  treatment.  It  is  a  mistake  to  fix  any 
maximum  or  minimum  limits  to  the  final  dosage.  Some  authorities 
endeavour  always  to  reach  i  c.c.  of  old  tuberculin ;  others  are  content 
with  a  tenth  or  less  of  this  amount.  In  all  cases  where  auto-inoculatory 
symptoms  have  been  marked  and  where  tolerance  has  shown  a  tendency 
to  rapid  fall  it  is  very  desirable  to  establish  a  high  degree  of  tolerance 
by  reaching  a  dosage  of  i  c.c.  of  undiluted  tuberculin  if  possible. 
In  other  cases  the  lower  limit  of  o*i  c.c.  may  be  ample  or  it  may  even 
be  unnecessarily  high.  This  will  be  determined  by  the  general  features 
of  the  case  and  its  behaviour  during  the  course  of  specific  treatment. 
Objection  may  be  taken  to  my  scheme  for  the  conduct  of  treatment  on 
the  grounds  that  it  requires  too  great  individual  attention,  and  occupies 
more  time  than  can  possibly  be  devoted  to  any  case.  My  reply  to  this 
is  that  too  great  attention  cannot  possibly  be  given  to  the  individual 
peculiarities  of  any  case,  and  that  a  false  conception  may  easily  be 
formed  of  the  time  occupied  in  the  examinations  ;  while  it  is  true  that 
at  the  beginning  of  the  course  repeated  examinations  have  to  be  made 
at  short  intervals,  it  is  also  true  that  once  an  accurate  estimate  has  been 
formed  of  the  .reactive  powers  of  the  individual  it  is  possible  to  predict 
with  almost  unerring  accuracy  the  response  that  will  be  made  to  any 
dose;  it  therefore  follows  that  just  as  clinical  practice  enables  one  to 
make  a  careful  stethoscopic  examination  with  greatly  increased  speed, 
so  experience  of  the  patient  enables  one  to  foretell  the  appropriate  times 
for  such  examinations  to  be  made. 

I  will  now  pass  on  to  a  brief  description  of  the  methods  which  I 
consider  to  be  less  scientific  and  less  productive  of  clinical  benefit  than 
the  foregoing,  viz.  those  methods  wherein  the  guidance  utilised  is  that 
afforded  by  the  general  reaction  or  where  little  control  upon  dosage  is 
made  use  of  other  than  the  general  condition  of  the  patient.  In  this 
connection  three  different  schools  exist  :  (i)  That  including  Sahli, 
Denys  and  Wolff  -  Eisner,  who  aim  at  the  avoidance  of  all  general 
reactions.  (2)  That  including  Bandelier  and  Roepke  and  many  workers 
in  this  country  and  America,  who  aim  at  avoiding  all  excessive  reactions 
but  at  utilising  mild  ones.  (3)  That  including  Gotsch,  Moller,  Lowen- 
stein  and  Wilkinson,  who  pay  little  or  no  regard  to  strong  reactions, 
and  regard  them  as  inevitable  and  as  useful  stepping-stones  to  the 
attainment  of  a  very  high  degree  of  tolerance.  The  first  of  these 
schools  hold  that  time  is  of  little  consequence  in  the  treatment  of  a 
disease  like  pulmonary  tuberculosis,  which,  as  a  rule,  progresses  so 
slowly.  They  are  still  more  or  less  obsessed  by  the  memory  of  the 
disasters  of  early  days,  and  would  avoid  any  possibility  of  producing  a 


THE   BACTERIAL    DISEASES   OF    RESPIRATION.  22/ 

reaction  which  might  have  even  the  most  temporary  ill-effects,  oblivious 
of  the  fact  that  improvement  in  some  cases  dates  only  from  the  time 
at  which  a  general  reaction  of  moderate  degree  was  first  excited,  and 
that  improvement  in  most  of  their  cases  begins  with  that  dosage  which 
just  fails  to  produce  a  general  reaction ;  in  other  words,  with  a  dosage 
that  in  the  great  majority  of  cases  produces  that  definite  focal  reaction 
which  was  not  excited  by  some  or  many  of  the  preceding  smaller  doses. 
Their  view  that  focal  reactions  are  not  induced  under  their  scheme  of 
treatment  is  explicable  only  on  the  assumptions  that  their  stethoscopic 
observations  are  not  sufficiently  complete  or  painstaking,  not  continued 
as  the  dosage  rises,  or  not  conducted  at  appropriate  intervals  after  the 
administration  of  the  tuberculin.  In  these  particulars  exception  is  to 
be  taken  to  Sahli's  methods,  and  many  will  not  agree  that  the  loss  of 
time,  whereby  a  course  of  treatment  is  drawn  out  to  one,  two  or  more 
years,  is  a  negligible  consideration ;  otherwise  much  is  to  be  said  for  a 
practice  wherein  great  regard  is  paid  otherwise  to  individual  peculiarities 
in  reactivity  and  wherein  danger  of  ill-effects  is  reduced  to  a  minimum. 
The  plan  of  treatment  is  to  begin  with  the  smallest  dose  of  one  of  the 
weakest  solutions  [e.g.  '05  c.c.  of  an  8ig2-fold  or  even  greater  dilution 
of  Beraneck's  tuberculin),  which  will  always  prove  harmless,  and  then 
the  dose  is  raised  quite  gradually  in  such  a  way  that  no  manifest  toxic 
actions  (so-called  reactions)  ever  occur,  or  if  these  are  not  to  be  avoided 
entirely  they  must  be  reduced  to  a  minimum.  As  soon  as  any  such 
phenomena  occur,  be  they  ever  so  insignificant,  one  must  wait  till  they 
entirely  disappear,  and  reduce  the  next  dose  to  at  least  one  half  of  that 
which  last  failed  to  produce  any  reaction  ;  the  interval  between  the 
doses  must  also  be  increased  and  the  treatment  subsequently  conducted 
with  greater  precautions.  Inoculations  are  given  not  oftener  than  twice 
a  week  with  the  concentrations  up  to  the  32-fold  dilution ;  thereafter 
only  once  a  week  till  the  maximum  dose  is  reached,  when  they  are  given 
only  once  a  fortnight. 

The  dosage  is  gradually  raised  by  yV  or  w  c.c.  of  each  dilution  till 
one  reaches  either  the  absolute  maximum  dose  of  i  c.c.  of  undiluted 
tuberculin,  or  if  the  sensitiveness  of  the  patient  will  net  permit  of  this, 
till  the  individual  maximum  dose  is  attained.  This  must  be  found  for 
each  separate  case ;  it  will  be  one  that  can  be  tolerated  without  any 
ill-effects,  but  cannot  be  exceeded  without  producing  unfavourable 
results.  When  this  individual  maximum  dose  has  once  been  reached, 
it  is  repeated  at  certain  intervals  but  not  exceeded. 

By  making  a  series  of  dilutions  in  multiples  of  2,  in  such  numbers 
that  a  dilution  of  65,536  times  is  ultimately  reached,  and  by  means  of 
the  device  of  using  only  the  upper  half  of  the  syringe  in  passing  from 
one  dilution  to  another,  so  that,  for  instance,  the  next  dose  following 

I5§ 


228  THE   BACTERIAL   DISEASES    OF    RESPIRATION. 

I  c.c.  of  dilution  Y^-g-  is  0*55  c.c.  of  dilution  J^,  Sahli  has  devised  a  very 
carefully  graduated  scheme  for  dosage,  which  certainly  has  advantage 
over  the  decimal  system  of  dilution  usually  employed. 

Bandelier  and  Roepke  and  the  other  members  of  the  second  school, 
while  not  failing  to  recognise  that  the  observance  of  symptoms  must 
also  be  supplemented  by  physical  examination  of  the  chest,  and  that 
focal  reactions  are  more  easily  produced  than  general  ones,  yet  fail  to 
utilise  this  knowledge  to  the  full  advantage.      Thus,  after  pointing  out 
that  "the  view   must  be  entirely  put  on   one  side  that  the  curative 
process  in  tuberculin  treatment  takes  place  only  with  objective  signs  of 
reaction,"  and  that  "  clinical  observation  teaches  that  a  local  effect  on 
the  focus  of  disease  may  make  itself  evident  without  a  subjective  feeling 
of  illness  or  appreciable  rise  of  temperature,"  Bandelier  and  Roepke 
state  that  "  the  common  practice  of  observing  the  temperature  curve 
only  is  quite  sufficient  for  the  purpose,"  i.  e.  of  controlling  of  tuberculin 
inoculations.     They  hold  that    "  the    maxim   to    remain    as    close    as 
possible  to  the  reaction  limit  without  well-marked  or  severe  reactions 
occurring  coincides  with   the  experience  that  the  most  evident  results 
have  been  obtained  with  slight  reactions  up  to  38°  C.  or  a  little  over. 
The  principle  of  the  production  of  slight  reactions  will  be  more  in  place 
and  easier  to<:arry  out  in  slighter  and  more  limited  cases  of  disease,  in 
the  slowly  progressive  forms  associated  with  fibrosis,  where  nutrition  and 
appetite  are  good,  where  weight  is  being  put  on  and  the  temperature 
normal,  and  where  susceptibility  to  tuberculin  is  slight.      But  in  these 
cases  the  possibility  of  an  overdose  must  still  be  borne  in  mind."    And 
again,  "  It  must  be  constantly  kept  in  mind  that  the  curative  effect  for 
the  individual  is  dependent,  not  on  the  absolute,  but  on  the  relative  size 
of   the  dose,   i.  e.  that   quantity  of  tuberculin    is  most  advantageous 
which  can  at  anytime  be  just  borne  without  (general)  reaction.     .     .     . 
Time  must  be  allowed  for  the  increase  of  dosage,  and  the  same  dose 
repeated,  if  necessary,  several  times  if  reaction  occurs,  with  increase  of 
the  interval ;  or  better,   a  return   made  to  a  smaller  dose,  increased 
again  more  slowly.     The  thought  guiding  action  must  be  that  any  dose 
associated  with  fever  is  too  high  for  the  individual  concerned,  and  that 
the  smaller  dose  borne  without  reaction  not  merely  suffices  for  thera- 
peutic action  but  is  actually  of   more   value.     Tolerance  cannot    be 
attained  by  violence  but  only  by  patiently  persisting."     The  obvious 
criticism  of  all  this  is  that  while  strongly  upholding  the  advisability  of 
a  dosage  which  just  falls  short  of  a  reaction  in  practice  they  fail  to 
follow  out  their  own  precepts,  and  only  determine  the  magnitude  of 
their  dosage   by    producing  such   reactions — at  all  events  from  time 
to  time.     Were  more  attention  paid  in  the  way  I  have  indicated  to  the 
resulting  focal  reactions,  which  they  themselves  admit  are  produced  by 


THE    BACTERIAL    DISEASES    OF   RESPIRATION.  229 

dosages  which  fail  to  excite  general  reactions,  guess-work  and  improper 
experimental  determinations  would  be  no  longer  necessary.  In 
practice  the  determination  of  the  dosage  just  short  of  that  which  will 
produce  a  general  reaction  is  facilitated  by  the  observation  that  a 
definite  flattening  of  the  temperature  is  coincident  with  the  approach  of 
the  limit  of  tolerance.  As  regards  the  conclusion  of  treatment  they 
write  :  "  It  must  be  our  aim  to  attain  to  the  highest  possible  doses  of 
tuberculin,  to  reach  the  maximal  dose.  In  slight  cases  a  cure  will  be 
effected  in  this  way.  If  the  limit  of  apparently  possible  improvement 
is  not  then  reached  the  maximal  dose  is  to  be  repeated  at  increasing 
intervals  as  long  as  improvement  continues,  in  order  to  retain  the  toxic 
immunity  as  long  as  may  be,  to  stimulate  the  production  of  antibodies 
and  to  assist  the  healing  processes.  This  injection  of  the  absolute 
maximum  we  have  ourselves  prolonged  for  many  months."  Sahli  well 
points  out  how  utterly  illogical  is  this  artificial  creation  of  a  maximum 
dose  at  the  containing  capacity  of  the  ordinary  syringe,  for  this  alone 
is  the  real  reason  why  the  maximum  of  dosage  has  been  fixed  at  i  c.c. 
The  objection  is,  however,  deprived  of  most  of  its  sting  in  virtue  of  the 
fact  that  most  members  of  this  school  stop  considerably  short  of  i  c.c. 
as  the  maximum  dose. 

The  procedures  of  the  third  school,  that  which  ignores  reactions 
and  regards  them  as  an  incidental  inevitable  to  a  course  of  tuberculin, 
are  based  on  the  following  considerations :  (i)  that  the  constitutional 
disturbances  of  the  disease  are  due  to  lack  of  toxin  tolerance  on  the 
part  of  the  tissues  ;  (2)  that  general  reactions,  like  the  constitutional 
disturbances,  are  unwelcome,  and  are  obstacles  to  the  attainment  of 
the  desired  tolerance  ;  (3)  that  therefore  they  are  to  be  swept  aside  and 
overcome  by  brute  force,  as  they  have  found  can  be  done  by  the 
administration  of  massive  doses,  which  must  act  by  paralysing  the 
mechanism  of  reactivity.  They  therefore  waste  no  time,  but  begin 
with  doses  of  "0002  c.c.  of  old  tuberculin,  increase  the  dosage,  if  neces- 
sary, till  a  general  reaction  is  the  result ;  when  this  occurs  they  repeat 
that  dosage  till  the  reaction  begins  to  fail,  when  once  more  the  dosage 
is  increased.  Some  stop  at  a  maximal  dose  of  i  c.c,  others  do  not 
hesitate  to  go  beyond  this  limit.  In  the  case  of  some  of  this  school 
the  treatment  is  begun  with  P.T.O.  ;  when  a  dosage  of  i  c.c.  has  been 
attained  with  this,  P.T.  is  substituted  for  it,  treatment  being  concluded 
with  a  course  of  old  tuberculin. 

The  objections  to  this  method  are  several:  (i)  it  is  really  only 
applicable  to  those  whose  general  condition  warrants  such  severe  and 
oft-repeated  constitutional  disturbances ;  (2)  that  even  in  these  the 
reactions  may  become  more  than  the  sufferers  can  bear,  and  treatment 
is  abandoned ;  (3)   that  cases  of  mixed  infection  are  considered  to  be 


230  THE   BACTERIAL    DISEASES    OF   RESPIRATION. 

unsuited  to  the  treatment,  and  these  comprise  a  very  considerable 
proportion  of  the  phthisical ;  (4)  in  advanced  cases  with  pyrexia  more 
harm  than  good  may  result. 

There  are  other  means  of  moving  a  heavy  rock  than  by  means  of  a 
cumbrous  crane — a  lever  will  do  the  same  work  with  much  less  ex- 
penditure of  energy  and  sometimes  more  expeditiously;  similarly 
there  are  ways  of  raising  tolerance  than  by  the  sledge-hammer-like 
blows  of  massive  dosage.  On  the  other  hand,  there  is  at  least  one 
class  of  case  to  which  this  method  is  the  more  applicable,  namely,  those 
cases  of  good  general  condition  who,  despite  moderate  degrees  of 
pyrexia,  have  to  go  about  their  daily  work,  means  of  undergoing  a 
careful  course  of  immunisation  in  sanatorium  or  their  own  home 
being  quite  beyond  them.  Such  cases  are  undergoing  constant  auto- 
inoculation  with  varying  doses  of  tuberculin  at  irregular  intervals. 
The  rest  in  bed  which  would  control  these  being  denied  the  patient, 
it  becomes  urgently  necessary  to  overwhelm  these  irregular  disturbances, 
which  are  unsuitable  as  stimuli  for  the  establishment  of  immunity, 
under  the  greater  and  regulated  waves  set  up  by  massive  doses  of 
tuberculin.  That  this  objective  is  by  no  means  impossible  of  attain- 
ment is  certainly  shown  by  the  statistics  of  Wilkinson,  Lowenstein  and 
Gotsch,  and  if  this  method  be  regarded  as  one  to  be  employed  in  the 
lack  of  opportunity  to  the  employment  of  a  better,  a  definite  sphere 
of  usefulness  can  be  assigned  to  it ;  it  may  even  be  regarded  as  the 
method  of  election  for  use  on  ambulatory  patients,  adapted  to  the  needs 
and  requirements,  not  of  the  classes,  but  of  the  masses. 

Treatment  by  the  Induction  of  Auto-inoculations. 

Inman   and   Paterson  have   carefully  investigated  the  relationship 
of    the   temperature    curve    to   that    of   the    opsonic    content    of   the 
serum    in    pyrexial    cases    of  phthisis.       They   found   that   the    two 
curves   roughly  correspond   but    move    in   reverse  directions.      From 
this  it  may  be   inferred  that  rise  of  temperature  corresponds  to  fall 
in   content  of  the  immune  bodies  generally  of  the  blood,  and    that 
control    of   the    temperature    oscillations   would  result    in  the  main- 
tenance of  the  defensive  mechanism  at  a  steadier  level.     This  has  been 
confirmed  by  clinical  observation ;   cases  of  irregular  pyrexia  wh  ich 
are   taking   a   downhill   course  improve  markedly  when  the  pyrexia 
is  controlled  by  rest  in  bed.     Sometimes  ordinary  rest  will  achieve  this 
end  ;  sometimes  absolute  or  "  typhoid"  rest  is  essential ;  occasionally 
no  degree  of  rest  will  control  the  irregular  auto-inoculations.     The 
thought  suggested  itself  to  Paterson  whether  it  would  not  be  better  to 
utilise  inoculations  with  the  patient's  own    tuberculin  produced   by 


THE    BACTERIAL   DISEASES    OF    RESPIRATION.  23  I 

increasing  the  vascular  supply  to  the  infected  foci  by  means  of  care- 
fully ordered  exercise  than  to  introduce  tuberculin  from  without.  The 
very  large  percentage  of  the  human  race  who  do  successfully  auto- 
inoculate  themselves  lends  an  a  priori  support  to  an  affirmative  answer. 
Paterson  has  therefore  given  an  extensive  trial  to  the  treatment  of 
cases  of  pulmonary  tuberculosis  by  carefully  graduated  rest  and  exercise. 
Cases  with  pyrexia  are  sent  to  bed  and  kept  at  rest,  ordinary  or  "typhoid," 
until  their  pyrexia  is  under  complete  control ;  they  are  then  allowed 
up  and  given  carefully  graduated  exercise.  If  the  exercise  results  in  a 
rise  of  temperature  to  over  99°  F.  they  are  kept  at  rest  until  the  tem- 
perature has  steadied  itself  once  more,  when  exercise  is  again  per- 
mitted, and  so  on.  In  this  way  it  is  found  that  the  organism  can  be 
accustomed  to  more  and  more  exercise,  until  finally  a  hard  day's  manual 
labour  may  fail  to  elicit  an  immunising  response  as  evidenced  by  rise 
of  temperature  beyond  the  patient's  normal.  The  treatment  has  been 
found  to  be  especially  beneficial  to  cases  which  show  little  pyrexia  and 
fail  to  improve  beyond  a  certain  point.  Paterson  reports  excellent 
results  from  this  form  of  treatment,  but  there  are  several  objections  to 
be  taken  to  it :  (i)  It  necessitates  great  individual  attention  and  con- 
siderable care  and  judgment  on  the  part  of  the  physician  in  the  assign- 
ment of  the  exercise  to  be  taken  by  each  patient.  (2)  It  can  only  be 
carried  out  in  a  well-ordered  sanatorium  where  the  opportunity  exists 
for  furnishing  the  necessary  tasks  to  the  patients.  (3)  Auto-inocula- 
tions are  induced  the  most  easily  when  they  are  least  desired,  and  are 
most  difficult  to  induce  when  they  are  the  most  to  be  desired ;  i.  e.  as 
treatment  advances,  and  arrest  and  cure  are  the  more  nearly  reached, 
the  organism  gradually  accustoms  itself  to  stimuli,  so  that  to  keep  up  a 
high  degree  of  immunity  stimuli  of  increasing  strength  must  needs  be 
applied.  On  the  other  hand,  as  healing  of  the  foci  proceeds  the  difficulty 
of  inducing  hypersemia  in  them  increases,  and  the  quantum  of  bacilli  and 
their  products  which  are  carried  into  the  circulation  shows  a  corre- 
sponding decrease.  It  thus  comes  about  that  while  it  is  easy  to  bring 
about  marked  relief  of  constitutional  S3'mptoms  and  rise  in  tolerance,  it 
is  rather  more  difficult  to  bring  about  arrest  and  much  more  difficult  to 
bring  about  a  cure. 

It  is  much  to  be  regretted  that  Paterson  appears  to  have  contented 
himself  with  an  imperfect  ideal,  that  he  is  content  with  having  produced 
that  degree  of  improvement  which  will  enable  the  patient  to  return  to 
his  daily  task,  however  severe  this  may  be,  without  any  resultant  con- 
stitutional disturbance. 

To  the  disappearance  of  all  bacilli  from  the  sputum,  to  the  precise 
condition  of  the  infected  foci  and  consequently  to  the  chance  of 
permanence   o£  the  results  obtained  he  appears  to  have  paid  too  little 


232  THE   BACTERIAL    DISEASES   OF   RESPIRATION. 

heed.  The  procedure  is  based  on  sound  reasoning  and  sound  observation, 
and  the  introduction  into  it  of  suitable  modifications,  such  as  the  addition 
of  stimuH  from  without  as  those  from  within  begin  to  fail,  would  tend  to 
widen  its  applicability  and  increase  its  value.  Whether  auto-inoculatory 
procedures  can  be  conducted  with  benefit  in  cases  of  mixed  infection  is 
very  doubtful  and  must  be  left  to  the  future  to  decide. 

Residts. 

Upon  this  question  I  propose  to  say  but  little.  Mere  statistics  are  of 
little  help  in  aiding  the  formation  of  a  true  estimate  of  the  value  of 
tuberculin  in  the  treatment  of  pulmonary  tuberculosis.  The  disease  is 
often  a  very  chronic  one,  and  one  of  its  worst  features  is  its  crippling 
effect  on  man's  power  of  work  and  of  production,  and  the  consequent 
casting  of  his  maintenance  upon  the  shoulders  of  others.  From  the 
economic  standpoint  it  is  therefore  even  more  important  that  recovery 
should  be  expedited  in  those  who  are  destined  in  any  case  to  recover,  than 
that  a  certain  additional  percentage  should  be  preserved  to  lead  a  life  of 
semi-invalidism. 

One  of  the  most  striking  testimonies  to  the  value  of  tuberculin 
treatment  is  the  complete  change  of  front  in  regard  to  its  use  which  has 
once  more  come  over  the  medical  men  throughout  the  world.  Riviere 
and  Morland  point  out,  that  whereas  the  percentage  of  sanatoria  and 
public  institutions  in  Germany  which  combined  specific  with  hygienic 
treatment  was  only  29  in  1905,  it  had  risen  to  57  in  1907  and  to  about  70 
in  1910.  Many  lung  specialists  who  formerly  were  utterly  opposed  to 
it  now  use  it  extensively.  Bandelier  and  Roepke  cite  the  remarkable 
instance  of  Ritter,  who,  prejudiced  against  tuberculin,  wished  to  collect 
evidence  of  its  inefficacy.  He  therefore  treated  at  his  sanatorium  a 
number  of  cases  which  had  already  undergone  treatment  without  avail. 
The  result  is  seen  in  the  views  he  expressed  in  1908,  that  sanatorium 
physicians  are  not  merely  justified,  but  in  a  certain  sense  bound  to  make 
the  widest  possible  use  of  tuberculin  in  the  treatment  of  pulmonary 
tuberculosis. 

Sahli  says  as  regards  himself:  "  Blind  enthusiasm  for  tuberculin 
treatment  can  hardly  be  laid  to  my  charge,  but  I  honestly  believe 
that  it  is  the  best  weapon  of  modern  times  in  the  fight  against 
tuberculosis." 

The  greater  the  experience  of  most  specialists,  not  necessarily  in 
the  uses  of  tuberculin,  but  in  the  manifold  aspects  of  the  disease  itself, 
the  stronger  as  a  rule  is  their  advocacy  of  the  remedy  ;  the  greater  the 
experience  of  any  specialist  in  tuberculin  treatment  itself  the  stronger 
as  a   rule  is  their   advocacy,  not  that  its  use  should  be  confined  to 


THE    BACTERIAL   DISEASES    OF    RESPIRATION.  233 

specialists  like  themselves,  but  that  it  should  be  extended,  and  that  all 
general  practitioners  should  learn  to  avail  themselves  of  its  help.  Thus 
Sahli,  Bandelier  and  Roepke  and  Wilkinson  each  voice  this  sentiment, 
and  Lenhartz  expressed  much  the  same  view  when  he  said :  "  It  is  a 
defect  in  practice  when  tuberculin  is  not  employed." 

Riviere  and  Morland  sum  up  the  case  for  tuberculin  succinctly  and 
well  in  the  following  words :  "  But  statistics  apart,  certain  results  may 
be  said  to  be  well  established  by  clinical  experience.  The  first  and 
most  striking  of  these  is  that  phthisis  treated  with  tuberculin  before  it 
has  become  open  remains  closed.  The  importance  of  this  fact,  in 
which  there  is  practically  unanimous  opinion,  can  hardly  be 
exaggerated.  It  is  true  that  the  same  result  has  been  claimed  for 
hygienic  treatment ;  it  is  also  true  that  the  vis  medicatrix  naturcB 
unfettered  by  art  would  have  had  the  same  result  in  a  large  proportion 
of  cases  ;  but  there  remains  a  proportion — it  may  be  small — of  closed 
pulmonary  tuberculoses  which  will  not  get  well,  and  with  these  tuber- 
culin has  been  shown  to  be  competent  to  deal.  Early  diagnosis — that 
is  to  say,  really  early  diagnosis,  before  tubercle  bacilli  appear  in  the 
sputum — combined  with  specific  treatment,  insures  completely  against 
a  breakdown.  We  believe  that  statistics  have  already  shown  the 
ability  of  tuberculin  to  increase  the  percentage  of  those  who  lose  their 
sputum,  or  the  tubercle  bacilli  contained  in  it,  during  hygienic  treat- 
ment, and  to  extend  the  expectation  of  working  efficiency  after  hygienic 
treatment  ;  but  we  are  content  to  leave  this  to  a  more  rigid  demonstra- 
tion. Of  all  these  matters  the  tubercular  patient  is  the  final  judge, 
and  misled  as  he  was  by  the  disasters  of  i8go-gi,  there  is  no  doubt  that 
his  experience  of  tuberculin  under  the  new  conditions  is  making  him 
willing,  and  sometimes  even  anxious,  to  submit  himself  to  treatment 
with  the  remedy." 

It  is  with  the  earnest  hope  that  the  many  hours  of  patient  work 
which  I  have  bestowed  upon  the  various  forms  of  bacterial  invasion  of 
the  respiratory  tract  may  not  have  failed  to  cast  some  light  upon  the 
origin,  prophylaxis  and  treatment  of  the  various  distressing  manifesta- 
tions of  infection  and  of  pulmonary  tuberculosis  in  particular,  and 
thereby  may  have  contributed  in  some  small  measure  to  the  relief  of 
human  suffering,  that  I  leave  this  record  to  the  kindly  consideration  of 
the  reader. 


INDEX. 


Abscess  of  lung,  119 

Accessory  sinuses,  bacteriology  of,  47 

—  —  treatment  of,  87 
Albumen  test,  12 
AUergie,  202 
Antiformin  method,  20 

Antral  disease,  bacteriology  of,  47 

—  —  treatment  of,  87 
Asthma,  bacteriology  of,  52 

—  treatment  of,  97 
Auto-inoculation  in  phthisis,  230 

Bacillus,  Bordet-Gengou,  31 

—  coli  communis,  40 

—  diphtherise,  32 
— ■  Friedlander's,  38 

—  Hoffmann's,  32 

—  influenzae,  31,  74 

—  Koch-Weeks',  31 

—  proteus,  39 

—  pyocyaneus,  39 

—  septus,  32 

—  tuberculosis,  20,  25,  192 

—  typhosus,  40 

—  xerosis,  32 
Bacteriology  of  asthma,  52 

—  bronchitis,  52 

—  catarrh,  nasal,  44 

—  —  post-nasal,  46 

—  common  cold,  44 

—  laryngitis,  51 

—  ozsena,  137 

—  phthisis,  55,  145 

—  pneumonia,  104 

—  rhinoscleroma,  139 

—  sinusitis,  47 

—  tracheitis,  51 

—  whooping-cough,  55,  122 
Blister  test.  Woodcock's,  204 
Blood-agar,  23 

Blood  cultures,  106 


Bronchitis,  bacteriology  of,  52 

—  treatment  of,  90 
Broncho-pneumonia,  119 

Calmette's  test,  206 
Capsule  staining,  21 
Catarrh,  Eustachian,  50 

—  general  treatment  of,  82 

—  post-nasal,  46 

—  nasal,  44 

—  vaccine  treatment  of,  71,  79 
Cells  of  sputum,  13 

Chemical  examination  of  sputum,  ii 
Cultural  methods,  23 

Diphtheria  bacillus,  32 

—  treatment  of,  123 

Dosage,  control  of,  65,  Bo,  91,  156 

Empyema,   119 

Flagella  staining,  21 
Focal  reaction,  210 
Friedlander's  bacillus,  38,  73 
Fusiform  bacillus,  41 

Gram's  method  of  staining,  18 

Hay-fever,  134 

Influenza  bacillus,  31,  74 
Inhalations,  188 
Intervals,  control  of,  65,  91 
Intra-dermal  test,  203 
Intra-tracheal  injection,  189 

Koch-Weeks'  bacillus,  31 

Laryngitis,  51,  83 
Leishman's  stain,  13,  20 
Lung  abscess,  119 

—  puncture    10 


236 


INDEX. 


Media,  23 

Meningococcus,  35 

Methods  of  collecting  material,  8 

—  of  staining,  12,  17 
Micrococcus  catarrhalis,  33,  72 

—  paratetragenus,  37,  72 

—  tetragenus,  37 

Mixed  infection,  import  of,  141,  147 

—  —   prevention  of,  180 

treatment  of,  160,  170 

Morro's  test,  204 

Nasal  catarrh,  bacteriology  of,  44 

—  —  treatment  of,  71,  79 

Ophthalmo-test,  206 

Opsonic  index  in  diagnosis,  214 

Ozasna,  bacteriology  of,  137 

—  treatment  of,  138 

Percutaneous  test,  204 

Phthisis,  bacteriology  of,  55,  145 

—  mixed  infections  of,  55,  141 

—  treatment  of ,  140,  192 
Pneumococcus,  30,  73 
Pneumonia,  bacteriplogy  of,  104 

—  pathology  of,  107 

—  prophylaxis  of,  107 

—  treatment  of,  103 

Post-nasal  catarrh,  bacteriology  of,  46 
• —  —  treatment  of,  84 
Preparation  of  vaccine,  75 
Prophylaxis  of  catarrhs,  84,  180,  1S7 

—  of  pneumonia,  107 

Pyorrhoea  alveolaris,  bacteriology  of,  41 

—  —  importance  of,  61,  125 

—  —  treatment  of,  124 

Reactions,  69,  80,  91,  156 

—  table  of,  69 

—  to  tuberculin,  202 
Reactivity,  202,  211 
Rhinoscleroma,  bacteriology  of,  139 

—  treatment  of,  139 

Salicylate  test,  1 1 

Sero-albuminous  contents  of  sputum,  16 

Sinusitis,  bacteriology  of,  47 

—  treatment  of,  87 
Spengler's  staining  methods,  19 


Sputum,  cells  of,  13 

—  chemical  examination  of,  11 

—  method  of  collecting,  9 
Staphylococcus,  27 
Streptococcus, 28,  74 
Streptothrix,  25 
Subcutaneous  test,  207 
Swabs,  method  of  taking,  8 

Tonsillitis,  bacteriology  of,  41 

—  treatment  of,  62 
Tracheitis,  51 

Tubercle  bacillus,  cultivation  of,  25 

—  —  isolation  of,  20,  25 

—  —  staining  of,  18 
Tuberculin,  choice  of,  219 

—  in  diagnosis,  202 

—  in  treatment,  221 

—  reaction,  207 
Tuberculins,  the,  199 

Tuberculosis,  defensive  mechanism   against, 
196 

—  mixed  infection  in,  56,  140,  160,  170,  180, 

—  treatment  of,  140,  192 

Unna's  methylene-blue,  13 

Vaccine,  administration  of,  77 

—  preparation  of,  75 

—  treatment  of  asthma,  97 

—  —  of  bronchitis,  90 

■ —  —  of  catarrhs,  71,  79 

—  —  of  diphtheria,  123 

—  —  of  hay-fever,  134 

—  —  of  mixed  infections,  160,  170 

—  —  of  ozasna,  138 
of  phthisis,  140,  192 

—  —  of  pneumonia,  103 

of  pyorrhoea  alveolaris,  124 

of  rhinoscleroma,  139 

—  —   of  sinusitis,  87 

—  —  of  whooping-cough,  121 

—  —  preliminaries  to,  58 

—  —  rationale  of,  62 
Von  Pirquet  test,  202 

Whooping-cough,  bacteriology  of,  55,  122 

—  treatment  of  121 
Woodcock's  blister  test,  204 

Ziehl-Neilsen's  staining  method,  18. 


